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Influence of Endogenous and Exogenous Effectors on the Pharmacokinetics of Theophylline

Focus on Biotransformation

  • Review Article
  • Drug Disposition
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Summary

Theophylline has been widely used as a bronchodilatory drug for the treatment of neonatal apnoea in premature newborns and patients with obstructive airways disease. The development of analytical equipment and procedures to determine the systemic concentration of theophylline renders it possible to improve the effectiveness of theophylline therapy and reduce the incidence of toxic and adverse effects. Since the beginning of the 1970s, endogenous and exogenous factors (e.g. age, blood pH, concomitant diseases and drug therapy, meal preparation procedures, nutritional habits, pregnancy, gender, smoking and, to a lesser extent, biorhythms), influencing nearly all parameters of theophylline pharmacokinetics have been described.

Drug absorption depends on galenic formulation, drug delivery, nutritional habits and the chemical derivatives used. The mean plasma protein binding rates depend on the method of plasma protein determination: acidic blood pH values and advanced age may result in reduced plasma proteins. The volume of distribution depends primarily on age; it is 2-fold greater in newborns than in adults. Furthermore, changes in blood pH values, the plasma protein content and the administration of concomitant drugs may vary this parameter.

Biotransformation is the most clinically important pharmacokinetic parameter. Hepatic metabolism accounts for 90% of the metabolism of theophylline. Essentially, 2 microsomal isoenzymes of the cytochrome P450 system appear to be responsible for the N-methylation and 8-hydroxylation of the drug. Age and concomitant disease are the major endogenous effectors influencing biotransformation of theophylline, whereas biorhythms, gender and pregnancy are of lesser importance. Exogenous factors, such as concomitantly administered drugs, smoking and nutritional factors, affect biotransformation by inducing or inhibiting the metabolising enzymes.

Because of intra- and interindividual variability in the pharmacokinetics of theophylline, which may be increased by the presence of endogenous and/or exogenous effectors, it is necessary to supervise theophylline therapy by therapeutic drug monitoring if target concentrations are to be achieved.

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References

  1. Caldwell J, Cotgreave JA, Lawrie CA, et al. Origins of interindividual variations in theophylline metabolism in man. In: Rietbrock N, Woodcock BG, Staib AH, editors. Theophylline and other methylxanthines. Braunschweig: Fried Vieweg u. Sohn, 1982: 159–67

    Google Scholar 

  2. Hirsch S. Klinischer und experimenteller Beitrag zur krampflösenden Wirkung der Purinderivate. Klin Wochenschr 1922; 1: 615–8

    Article  Google Scholar 

  3. Scholz H. Pharmakologische Wirkungen von Theophyllin und ihre Mechanismen. In: Oellerich M, Sybrecht GW, Wettengel R, editors. Theophyllin — Optimierung der Therapie in Klinik und Praxis. Neu-Isenburg: IMP-Kommunikationsgesellschaft, 1983: 9–19

    Google Scholar 

  4. Hill MR, Szefler SJ. Theophylline update: current controversies. Semin Respir Med 1987; 8: 372–80

    Article  Google Scholar 

  5. Bukowskyj M, Nakatsu K, Munt PW. Theophylline reassessed. Ann Intern Med 1984; 101: 63–73

    PubMed  CAS  Google Scholar 

  6. Fredholm BB. On the mechanism of action of theophylline and caffeine. Acta Med Scand 1985; 217: 149–53

    Article  PubMed  CAS  Google Scholar 

  7. Hendeles L, Weinberger M. Theophylline: ‘a state of the art’ review. Pharmacotherapy 1983; 3: 2–44

    PubMed  CAS  Google Scholar 

  8. Herrmann G, Aynesworth MB. Successful treatment of persistent extreme dyspnoea ‘status asthmaticus’. J Lab Clin Med 1937; 23: 135–48

    Google Scholar 

  9. Jenne JW, Wyze MSE, Read FS, et al. Pharmacokinetics of theophylline; application to adjustment of the clinical dose of aminophylline. Clin Pharmacol Ther 1972; 13: 349–60

    PubMed  CAS  Google Scholar 

  10. Mitenko PA, Oglivie RJ. Rational intravenous doses of theophylline. N Engl J Med 1973; 289: 600–3

    Article  PubMed  CAS  Google Scholar 

  11. Kaumeier HS, Kehrhahn OH, Neugebauer G, et al. A cross-over study of oral and intravenous administration of theophylline in male volunteers (absolute bioavailability of Afonilum tablets). Int J Clin Pharmacol Ther Toxicol 1983; 21: 339–45

    PubMed  CAS  Google Scholar 

  12. Manfredi RL, Vesell ES. Inhibition of theophylline metabolism by long-term allopurinol administration. Clin Pharmacol Ther 1981; 29: 224–9

    Article  PubMed  CAS  Google Scholar 

  13. Steinijans VW, Eicke R, Ahrens J. Pharmacokinetics of theophylline in patients following short-term intravenous infusion. Eur J Clin Pharmacol 1982; 22: 417–22

    Article  PubMed  CAS  Google Scholar 

  14. Bachmann K, Schwartz J, Forney R, et al. Theophylline kinetics: dose dependency and single prediction of clearance. Pharmacology 1985; 30: 136–44

    Article  PubMed  CAS  Google Scholar 

  15. Dahlqvist R, Billing B. Pharmacokinetic properties of a new sustained-release theophylline preparation. Int J Clin Pharmacol Ther Toxicol 1983; 21: 69–72

    PubMed  CAS  Google Scholar 

  16. Tang-Liu DDS, Williams RL, Riegelman S. Nonlinear theophylline elimination. Clin Pharmacol Ther 1982; 31: 358–69

    Article  PubMed  CAS  Google Scholar 

  17. Koëter GH, Jonkman JHG, de Vries K, et al. Pharmacokinetics of sustained release theophylline in low and high multidose regimens. Br J Clin Pharmacol 1981; 12: 647–51

    Article  PubMed  Google Scholar 

  18. Rovei V, Chanoine F, Benedetti MST. Pharmacokinetics of theophylline: a dose-range study. Br J Clin Pharmacol 1982; 14: 769–78

    Article  PubMed  CAS  Google Scholar 

  19. Slotfeldt ML, Johnson CE, Grambau G, et al. Reliability of theophylline clearance in determining chronic oral dosage regimens. Am J Hosp Pharm 1979; 37: 66–8

    Google Scholar 

  20. Wagner JG. Theophylline — pooled Michaelis-Menten parameters (Vmax and Km) and implications. Clin Pharmacokinet 1985; 10: 432–42

    Article  PubMed  CAS  Google Scholar 

  21. Lesko LJ. Dose-dependent kinetics of theophylline in the treatment of chronic reversible airways obstruction. In: Jonkman JHG, Jenne JW, Simons FER, editors. Current clinical practice, Series No 8. Amsterdam: Excerpta Medica, 1984: 67–72

    Google Scholar 

  22. Reinhardt D, Richter O, Genz T, et al. Linear elimination kinetics but non-linear pharmacodynamics in theophylline intoxication in a child. Int J Clin Pharmacol Ther Toxicol 1982; 20: 171–3

    PubMed  CAS  Google Scholar 

  23. Vaucher Y, Lighter ES, Walson PD. Theophylline poisoning. J Pediatr 1977; 90: 827–30

    Article  PubMed  CAS  Google Scholar 

  24. Kraemer MJ, Furukawa CT, Koup JR, et al. Altered theophylline clearance during an influenza B outbreak. Pediatrics 1982; 69: 476–80

    PubMed  CAS  Google Scholar 

  25. Boutry MJ, Vert P, Royer RJ, et al. Caffeine, a metabolite of theophylline during the treatment of apnea in the premature infant. J Pediatrics 1979; 94: 996–8

    Article  Google Scholar 

  26. Brazier JL, Renaud H, Ribon B, et al. Evolution du taux plasmatique des xanthines dans le traitement de l’apnee du premature. Therapie 1978; 33: 341–55

    PubMed  CAS  Google Scholar 

  27. Giacoia G, Jusko WJ, Menke J, et al. Theophylline pharmacokinetics in premature infants with apnea. J Pediatrics 1976; 89: 829–32

    Article  CAS  Google Scholar 

  28. Gilman JT, Gal P, Levine RS, et al. Factors influencing theophylline disposition in 179 newborns. Ther Drug Monit 1986; 8: 4–10

    Article  PubMed  CAS  Google Scholar 

  29. Hilligos DM, Jusko WJ, Koup JR, et al. Factors affecting theophylline pharmacokinetics in premature infants with apnea. Dev Pharmacol Ther 1980; 1: 6–15

    Google Scholar 

  30. Latini R, Assael BM, Bonati M, et al. Kinetics and efficacy of theophylline in the treatment of apnea in the premature newborn. Eur J Clin Pharmacol 1978; 13: 203–7

    Article  PubMed  CAS  Google Scholar 

  31. Antal EJ, Kramer PA, Mercik SA, et al. Theophylline pharmacokinetics in advanced age. Br J Clin Pharmacol 1981; 12: 637–45

    Article  PubMed  CAS  Google Scholar 

  32. Vestal RE, Cusack BJ, Mercer GD, et al. Aging and drug interactions I. Effect of cimetidine and smoking on the oxidation of theophylline and cortisol in healthy men. J Pharmacol Exper Ther 1987; 241: 488–500

    CAS  Google Scholar 

  33. Au WYW, Dutt AK, DeSoyza N. Theophylline kinetics in chronic obstructive airway disease in the elderly. Clin Pharmacol Ther 1985; 37: 472–8

    Article  PubMed  CAS  Google Scholar 

  34. Jackson SHD, Johnston A, Woollard R, et al. The relationship between theophylline clearance and age in adult life. Eur J Clin Pharmacol 1989; 36: 29–34

    Article  PubMed  CAS  Google Scholar 

  35. Mühlberg W, Platt D, Bauer M, et al. Pharmakokinetik und Pharmakodynamik von Theophyllin bei multimorbiden geriatrischen Patienten. Klin Wochenschr 1987; 65: 551–7

    Article  PubMed  Google Scholar 

  36. Nielsen-Kudsk F, Magnussen I, Jakobsen P. Pharmacokinetics of theophylline in ten elderly patients. Acta Pharmacol Toxicol 1978; 42: 226–34

    Article  CAS  Google Scholar 

  37. Shin SG, Juan D, Rammohan M. Theophylline pharmacokinetics in normal elderly subjects. Clin Pharmacol Ther 1988; 44: 522–30

    Article  PubMed  CAS  Google Scholar 

  38. Horai Y, Ishizaki T, Sasaki T, et al. Bioavailability and pharmacokinetics of theophylline in plain uncoated and sustainedrelease dosage forms in relation to smoking habit, I. Single dose study. Eur J Clin Pharmacol 1983; 24: 79–97

    Article  PubMed  CAS  Google Scholar 

  39. Steinijans VW, Schulz HU, Böhm A, et al. Absolute bioavailability of theophylline from a sustained-release formulation using different intravenous reference infusions. Eur J Clin Pharmacol 1987; 33: 523–6

    Article  PubMed  CAS  Google Scholar 

  40. Aarbakke J, Høylandskjær A, Gamst ON. Serum theophylline levels after use of an anhydrous crystalline theophylline suppository. Eur J Clin Pharmacol 1981; 20: 449–52

    Article  PubMed  CAS  Google Scholar 

  41. Bolme P, Edlund PO, Eriksson M, et al. Pharmacokinetics of theophylline in young children with asthma: comparison of rectal enema and suppositories. Eur J Clin Pharmacol 1979; 16: 133–9

    Article  PubMed  CAS  Google Scholar 

  42. Aslaksen A, Bakke OM, Vigander T. Comparative pharmacokinetics of theophylline and aminophylline in man. Br J Clin Pharmacol 1981; 11: 269–73

    Article  PubMed  CAS  Google Scholar 

  43. Schulz HU, Steinijans VW, Gabel H. Differences in steady-state plasma levels between aminophylline and theophylline sustained-release micropellets after repeated circadian dosing. Int J Clin Pharmacol Ther Toxicol 1984; 22: 621–5

    PubMed  CAS  Google Scholar 

  44. Jonkman JHG, van der Boon WJV, Balant LP, et al. Food reduces the rate but not the extent of the absorption of theophylline from an aqueous solution. Eur J Clin Pharmacol 1985; 28: 225–7

    Article  PubMed  CAS  Google Scholar 

  45. Karim A, Burns T, Wearley, L, et al. Food-induced changes in theophylline absorption from controlled-release formulations. Part I. Substantial increased and decreased absorption with Uniphyl tablets and Theo-Dur Sprinkle. Clin Pharmacol Ther 1985; 38: 77–83

    Article  PubMed  CAS  Google Scholar 

  46. Lagas M, Jonkman JHG. Greatly enhanced bioavailability of theophylline on postprandial administration of a sustained release tablet. Eur J Clin Pharmacol 1983; 24: 761–7

    Article  PubMed  CAS  Google Scholar 

  47. Lagas M, Jonkman JHG. Influence of food on the rate and extent of absorption of theophylline after single dose oral administration of a controlled release tablet, Int. J Clin Pharmacol Ther Toxicol 1985; 23: 424–6

    CAS  Google Scholar 

  48. Gai MN, Thielemann AM, Arancibia A. Evaluation of the effect of different kinds of foods on the bioavailability of a sustained-release theophylline tablet. Int J Clin Pharmacol Ther Toxicol 1993; 31: 547–52

    PubMed  CAS  Google Scholar 

  49. Karim A, Burns T, Janky D, et al. Food induced changes in theophylline absorption from controlled-release formulations. Part II. Importance of meal composition and dosing time relative to meal intake in assessing changes in absorption. Clin Pharmacol Ther 1985; 38: 642–7

    Article  PubMed  CAS  Google Scholar 

  50. Schulz HU, Karlsson S, Sahner-Ahrens I, et al. Effect of drug intake prior to or after meals on serum theophylline concentrations: single-dose studies with Euphylong. Int J Clin Pharmacol Ther Toxicol 1987; 25: 222–8

    PubMed  CAS  Google Scholar 

  51. Shaw LM, Fields L, Mayock R. Factors influencing theophylline serum protein binding. Clin Pharmacol Ther 1982; 32: 490–6

    Article  PubMed  CAS  Google Scholar 

  52. Buss DC, Leopold D, Smith AP, et al. Determination of the plasma protein binding of theophylline in health. Br J Clin Pharmacol 1983; 15: 399–405

    Article  PubMed  CAS  Google Scholar 

  53. Vallner JJ, Speir Jr WA, Kolbeck RC, et al. Effect of pH on the binding of theophylline to serum proteins. Am Rev Respir Dis 1979; 120: 83–6

    PubMed  CAS  Google Scholar 

  54. Lesko LJ, Tabor KJ, Johnson BF. Theophylline serum protein binding in obstructive airways disease. Clin Pharmacol Ther 1981; 29: 776–81

    Article  PubMed  CAS  Google Scholar 

  55. Gal P, Jusko WJ, Yurchak AM, et al. Theophylline disposition in obesity. Clin Pharmacol Ther 1978; 23: 438–44

    PubMed  CAS  Google Scholar 

  56. Rizzo A, Mirabella A, Bonanno A. Effect of body weight on the volume of distribution of theophylline. Lung 1988; 166: 269–76

    Article  PubMed  CAS  Google Scholar 

  57. Rohrbaugh TM, Danish M, Rangni MC, et al. The effect of obesity on apparent volume of distribution of theophylline. Pediatr Pharmacol 1982; 2: 75–83

    CAS  Google Scholar 

  58. Jewesson PJ, Ensom RJ. Influence of body fat on the volume of distribution of theophylline. Ther Drug Monit 1985; 7: 197–201

    Article  PubMed  CAS  Google Scholar 

  59. Köhler E, Sollich V, Schuster R, et al. Theophyllinbestimmung im Speichel — eine Möglichkeit der non-invasiven Therapiekontrolle. Z Klin Med 1985; 40: 665–8

    Google Scholar 

  60. Moore ES, Faix RG, Banagale RC, et al. The population pharmacokinetics of theophylline in neonates and young infants. J Pharmacokinet Biopharm 1989; 17: 47–66

    PubMed  CAS  Google Scholar 

  61. Reinhardt D, Richter O, Brandenburg G. Pharmakokinetik des Arzneimittelübergangs von stillenden Müttern auf ihre Säuglinge am Beispiel des Theophyllins. Monatsschr Kinderheilkd 1983; 131: 66–70

    PubMed  CAS  Google Scholar 

  62. Richter O, Reinhardt D, Stutzinger W. Problematik der Entwicklung von Dosierungsschemata für medikamentöse Behandlungen im Kindesalter. Monatsschr Kinderheilkd 1983; 131: 63–5

    PubMed  CAS  Google Scholar 

  63. Resar RK, Walson PD, Fritz WL, et al. Kinetics of theophylline. Chest 1979; 76: 11–6

    Article  PubMed  CAS  Google Scholar 

  64. Mangione A, Imhoff TE, Lee RV, et al. Pharmacokinetics of theophylline in hepatic disease. Chest 1978; 73: 616–22

    Article  PubMed  CAS  Google Scholar 

  65. Piafsky KM, Sitar DS, Rangno RE, et al. Theophylline disposition in patients with hepatic cirrhosis. N Engl J Med 1977; 296: 1495–7

    Article  PubMed  CAS  Google Scholar 

  66. Conlon PF, Grambau GR, Johnson CE, et al. Effect of intravenous furosemide on serum theophylline concentration. Am J Hosp Pharm 1981; 38: 1345–7

    PubMed  CAS  Google Scholar 

  67. Jenne JW, Nagasawa HT, Thompson R. Relationship of urinary metabolites of theophylline to serum theophylline levels. Clin Pharmacol Ther 1976; 13: 375–81

    Google Scholar 

  68. Robson RA, Matthews AP, Miners JO, et al. Characterisation of theophylline metabolism in human liver microsomes. Br J Clin Pharmacol 1987; 24: 293–300

    Article  PubMed  CAS  Google Scholar 

  69. Robson RA, Miners JO, Matthews AP, et al. Characterisation of theophylline metabolism by human liver microsomes. Biochem Pharmacol 1988; 37: 1651–9

    Article  PubMed  CAS  Google Scholar 

  70. Birkett DJ, Miners JO, Attwood J. Secondary metabolism of theophylline biotransformation products in man — route of formation of 1-methyluric acid. Br J Clin Pharmacol 1983; 15: 117–9

    Article  PubMed  CAS  Google Scholar 

  71. Monks TJ, Smith RL, Caldwell J. A metabolic and pharmacokinetic comparison of theophylline and aminophylline (theophylline ethylenediamine). J Pharm Pharmacol 1981; 33: 93–7

    Article  PubMed  CAS  Google Scholar 

  72. Robson RA, Miners JO, Whitehead AG, et al. Specificity of the inhibitory effect of dextropropoxyphene on oxidative drug metabolism in man: effects on theophylline and tolbutamide disposition. Br J Clin Pharmacol 1987; 23: 772–5

    Article  PubMed  CAS  Google Scholar 

  73. Tserng KY, King KC, Takieddine FN. Theophylline metabolism in premature infants. Clin Pharmacol Ther 1981; 29: 594–600

    Article  PubMed  CAS  Google Scholar 

  74. Aranda JV, Louridas AT, Vitullo BB, et al. Metabolism of theophylline to caffeine in human fetal liver. Science 1979; 206: 1319–21

    Article  PubMed  CAS  Google Scholar 

  75. Tserng KY, Takieddine FN, King KC. Developmental aspects of theophylline metabolism in premature infants. Clin Pharmacol Ther 1983; 33: 522–8

    Article  PubMed  CAS  Google Scholar 

  76. Aranda JV, Rex J, Beharry K, et al. Theophylline metabolism in pre-school and pre-pubertal children, III. World Conference on Clinical Pharmacology and Therapeutics. Stockholm, Jul 27–Aug 1 1986: 405

  77. Jennings TS, Nafziger AN, Davidson L, et al. Gender differences in hepatic induction and inhibition of theophylline pharmacokinetics and metabolism. J Lab Clin Med 1993; 122: 208–16

    PubMed  CAS  Google Scholar 

  78. Aranda JV, Sitar DS, Parsons WD, et al. Pharmacokinetic aspects of theophylline in premature newborns. N Engl J Med 1976; 295: 413–6

    Article  PubMed  CAS  Google Scholar 

  79. Kraus DM, Fischer JH, Reitz SJ, et al. Alterations in theophylline metabolism during the first year of life. Clin Pharmacol Ther 1993; 54: 351–9

    Article  PubMed  CAS  Google Scholar 

  80. Reinhardt D. Theophyllin im Kindesalter. In: Oellerich M, Sybrecht GW, Wettengel R, editors. Theophyllin — Optimierung der Therapie in Klinik und Praxis. Neu-Isenburg: IMP-Kommunikationsgesellschaft, 1983: 141–56

    Google Scholar 

  81. Hill M, Haltom JR, Szefler SJ. The consistency of theophylline absorption from a sustained release formulation in asthmatic children. Pharmacotherapy 1988; 8: 277–83

    PubMed  CAS  Google Scholar 

  82. Ginchansky E, Weinberger M. Relationship of theophylline clearance to oral dosage in children with chronic asthma. J Pediatrics 1977; 91: 655–60

    Article  CAS  Google Scholar 

  83. Grygiel JJ, Ward H, Ogborne M, et al. Relationships between plasma theophylline clearance, liver volume and body weight in children and adults. Eur J Clin Pharmacol 1983; 24: 529–32

    Article  PubMed  CAS  Google Scholar 

  84. Roberts RK, Grice J, McGuffie C, et al. Oral contraceptive steroids impair the elimination of theophylline. J Lab Clin Med 1983; 101: 821–5

    PubMed  CAS  Google Scholar 

  85. Nafziger AN, Bertino Jr JS. Sex-related differences in theophylline pharmacokinetics. Eur J Clin Pharmacol 1989; 37: 97–100

    PubMed  CAS  Google Scholar 

  86. Jusko WJ, Gardner MJ, Mangione A, et al. Factors affecting theophylline clearances: age, tobacco, marijuana, cirrhosis, congestive heart failure, obesity, oral contraceptives, benzodiazepines, barbiturates and ethanol. J Pharm Sci 1979; 68: 1358–66

    Article  PubMed  CAS  Google Scholar 

  87. Bruguerolle B, Toumi M, Faraj F, et al. Influence of the menstrual cycle on theophylline pharmacokinetics in asthmatics. Eur J Clin Pharmacol 1990; 39: 59–61

    Article  PubMed  CAS  Google Scholar 

  88. Frederiksen MC, Ruo TI, Chow MJ, et al. Theophylline pharmacokinetics in pregnancy. Clin Pharmacol Ther 1988; 40: 321–8

    Article  Google Scholar 

  89. Parker WA. Effect of pregnancy on pharmacokinetics. In: Benet LZ, Massoud N, Gambertoglio JG, editors. Pharmacokinetic basis for drug treatment. New York: Raven Press, 1984: 249–57

    Google Scholar 

  90. Tornatore KM, Kanarkowski R, McCarthy et al. Effect of chronic oral contraceptive steroids on theophylline disposition. Eur J Clin Pharmacol 1982; 23: 129–34

    Article  PubMed  CAS  Google Scholar 

  91. Köhler E, Sollich V, Schuster R, et al. Untersuchungen zur Chronopharmakologie von Theophyllin unter therapeutischen Bedingungen bei Kindern und Erwachsenen. Z Klin Med 1990; 45: 1247–52

    Google Scholar 

  92. Jackson SHD, Johnston A, Woollard R, et al. Circadian variation in theophylline absorption during chronic dosing with a slow release theophylline preparation and the effect of clock time of dosing. Br J Clin Pharmacol 1988; 26: 73–7

    Article  PubMed  CAS  Google Scholar 

  93. Coulthard KP, Birkett DJ, Lines DR, et al. Bioavailability and diurnal variation in absorption of sustained release theophylline in asthmatic children. Eur J Clin Pharmacol 1983; 25: 667–72

    Article  PubMed  CAS  Google Scholar 

  94. Uematsu T, Follath F, Vozeh S. Circadian changes in the absorption and elimination of theophylline in patients with bronchial obstruction. Eur J Clin Pharmacol 1986; 30: 309–12

    Article  PubMed  CAS  Google Scholar 

  95. Jonkman JHG, van der Boon WJV, Balant LP, et al. Chronopharmacokinetics of theophylline after sustained release and intravenous administration to adults. Eur J Clin Pharmacol 1984; 26: 215–22

    Article  PubMed  CAS  Google Scholar 

  96. Jonkman JHG, Borgström L, van der Boon WJ, et al. Theophylline-terbutaline a steady state study on possible pharmacokinetic interactions with special reference to chronopharmacokinetic aspects. Br J Clin Pharmacol 1988; 26: 285–93

    Article  PubMed  CAS  Google Scholar 

  97. Reed RC, Schwartz HJ. Circadian variation in steady-state trough theophylline concentrations. Ther Drug Monit 1986; 8: 155–60

    Article  PubMed  CAS  Google Scholar 

  98. Vestal RE, Thummel KE, Mercer GD, et al. Comparison of single and multiple dose pharmacokinetics of theophylline using stable isotopes. Eur J Clin Pharmacol 1986; 30: 113–20

    Article  PubMed  CAS  Google Scholar 

  99. Staib AH, Schuppan D, Lissner R, et al. Pharmacokinetics and metabolism of theophylline in patients with liver diseases. Int J Clin Pharmacol Ther Toxicol 1980; 18: 500–2

    PubMed  CAS  Google Scholar 

  100. Cukier A, Strauss E, Filho T, et al. Theophylline metabolism in patients with hepatosplenic mansoniasis and cirrhosis. J Hepatol 1992; 15: 35–9

    Article  PubMed  CAS  Google Scholar 

  101. Kraan J, Jonkman JHG, Koëter GH, et al. The pharmacokinetics of theophylline and enprofylline in patients with liver cirrhosis and in patients with chronic renal disease. Eur J Clin Pharmacol 1988; 35: 357–62

    Article  PubMed  CAS  Google Scholar 

  102. Kuntz HD, Straub H, May B. Theophylline elimination in congestive heart failure. Klin Wochenschr 1983; 61: 1105–6

    Article  PubMed  CAS  Google Scholar 

  103. Piafsky KM, Sitar DS, Rangno RE, et al. Theophylline kinetics in acute pulmonary edema. Clin Pharmacol Ther 1977; 21: 310–6

    PubMed  CAS  Google Scholar 

  104. Vicuna N, McNaily JL, Ludden TM, et al. Impaired theophylline clearance in patients with cor pulmonale. Br J Clin Pharmacol 1979; 7: 33–7

    Article  PubMed  CAS  Google Scholar 

  105. Chang KC, Bell TD, Lauer BA, et al. Altered theophylline pharmacokinetics during acute respiratory viral illness. Lancet 1978; 1: 1132–3

    Article  PubMed  CAS  Google Scholar 

  106. Pokrajac M, Simic D, Varagic VM. Pharmacokinetics of theophylline in hyperthyroid and hypothyroid patients with chronic obstructive pulmonary disease. Eur J Clin Pharmacol 1987; 33: 483–6

    Article  PubMed  CAS  Google Scholar 

  107. Buss DC, Phillips DIW, Littley MD, et al. The effect of theophylline on thyrotoxic tremor. Br J Clin Pharmacol 1989; 28: 103–7

    Article  PubMed  CAS  Google Scholar 

  108. Dal Negro R, Turco P, Pomari C, et al. Effect of various disease on theophylline plasma levels and on pulmonary function in patients with chronic airway obstruction treated with a sustained release theophylline preparation. Int J Clin Pharmacol Ther Toxicol 1987; 25: 401–5

    Google Scholar 

  109. Jenne JW, Chick TW, Miller BA, et al. Apparent theophylline half-life fluctuations during treatment of acute left ventricular failure. Am J Hosp Pharm 1977; 24: 408–9

    Google Scholar 

  110. Renton KW. Effects of infection and immune stimulation on theophylline metabolism. Semin Perinatol 1981; 5: 378–82

    PubMed  CAS  Google Scholar 

  111. Williams SJ, Baird-Lambert JA. Inhibition of theophylline metabolism by interferon. Lancet 1987; 2: 939–41

    Article  PubMed  CAS  Google Scholar 

  112. Vozeh S, Otten M, Straub JJ, et al. Influence of thyroid function on theophylline kinetics. Clin Pharmacol Ther 1984; 36: 634–40

    Article  PubMed  CAS  Google Scholar 

  113. Reed RC, Schwarz HJ. Lack of influence of an intensive, antacid regimen on theophylline bioavailability. J Pharmacokinet Biopharm 1984; 12: 315–31

    PubMed  CAS  Google Scholar 

  114. Muir JF, Pfeiffer G, Richard MO, et al. Lack of effect of magnesium-aluminium hydroxide on the absorption of theophylline given as a pH-dependent sustained release preparation. Eur J Clin Pharmacol 1993; 44: 85–8

    Article  PubMed  CAS  Google Scholar 

  115. Oosterhuis B, Jonkman JHG, Andersson T, et al. No influence of single intravenous doses of omeprazole on theophylline elimination kinetics. J Clin Pharmacol 1992; 32: 470–5

    PubMed  CAS  Google Scholar 

  116. Taburet AM, Geneve J, Bocquentin M, et al. Theophylline steady state pharmacokinetics is not altered by omeprazole. Eur J Clin Pharmacol 1992; 42: 343–5

    Article  PubMed  CAS  Google Scholar 

  117. Schulz HU, Hartmann M, Steinijans VW, et al. Lack of influence of pantoprazole on the disposition kinetics of theophylline in man. Int J Clin Pharmacol Ther Toxicol 1991; 29: 369–75

    PubMed  CAS  Google Scholar 

  118. Cantral KA, Schaaf LJ, Jungnickel PW, et al. Effect of sucralfate on theophylline absorption in healthy volunteers. Clin Pharmacol 1988; 7: 58–61

    CAS  Google Scholar 

  119. Steeves RA, Robinson JD, McKenzie MW, et al. Effects of metoclopramide on the pharmacokinetics of a slow-release theophylline product. Clin Pharm 1982; 1: 356–60

    PubMed  CAS  Google Scholar 

  120. Adebayo GI, Mabadeje AFB. Lack of inhibitory effect of metronidazole on theophylline disposition in healthy subjects. Br J Clin Pharmacol 1988; 24: 110–3

    Article  Google Scholar 

  121. Schneider D, Gannon R, Sweeney K, et al. Theophylline and antiparasitic drug interactions: a case report and study of the influence of thiabendazole and mebendazole on theophylline pharmacokinetics in adults. Chest 1990; 97: 84–7

    Article  PubMed  CAS  Google Scholar 

  122. Garty M, Scolnik D, Danziger Y, et al. Non-interaction of ketotifen and theophylline in children with asthma — an acute study. Eur J Clin Pharmacol 1987; 32: 187–9

    Article  PubMed  CAS  Google Scholar 

  123. Hendy MS, Burge PS, Stableforth DE. Effect of ketotifen on the bronchodilating action of aminophylline. Respiration 1986; 49: 296–9

    Article  PubMed  CAS  Google Scholar 

  124. Hasegawa T, Takagi K, Kuzuya T, et al. Effect of mequitazine on the pharmacokinetics of theophylline in asthmatic patients. Eur J Clin Pharmacol 1990; 38: 255–8

    Article  PubMed  CAS  Google Scholar 

  125. Hasegawa T, Takagi K, Nadai M, et al. Kinetic interaction between theophylline and a newly developed antiallergic drug, pemirolast potassium. Eur J Clin Pharmacol 1994; 46: 55–8

    Article  PubMed  CAS  Google Scholar 

  126. Luskin SS, Fitzsimmons WE, MacLeod CM, et al. Pharmacokinetic evaluation of the terfenadine-theophylline interaction. J Allergy Clin Immunol 1989; 83: 406–11

    Article  PubMed  CAS  Google Scholar 

  127. Charles BG, Schneider JJ, Norris RLG, et al. Temelastine does not affect theophylline pharmacokinetics in normal subjects. Br J Clin Pharmacol 1987; 24: 673–5

    Article  PubMed  CAS  Google Scholar 

  128. Pfeifer HJ, Greenblatt DJ, Friedman P. Effect of antibiotics on theophylline kinetics in humans. Clin Pharmacol Ther 1978; 23: 124–5

    Google Scholar 

  129. Pfeifer H, Greenblatt DJ, Friedman P. Effects of three antibiotics on theophylline kinetics. Clin Pharmacol Ther 1979; 26: 36–40

    PubMed  CAS  Google Scholar 

  130. Bachmann K, Schwartz JI, Forney Jr RB, et al. Impact of cefaclor on the pharmacokinetics of theophylline. Ther Drug Monit 1986; 8: 151–4

    Article  PubMed  CAS  Google Scholar 

  131. Jonkman JHG, van der Boon WJV, Balant LP, et al. Clinical pharmacokinetics of theophylline during co-treatment with cefaclor. Int J Clin Pharmacol Ther Toxicol 1986; 24: 88–92

    PubMed  CAS  Google Scholar 

  132. Bachmann K, Schwartz J, Jauregui L, et al. Failure of ceftibuten to alter single dose theophylline clearance. J Clin Pharmacol 1990; 30: 444–8

    PubMed  CAS  Google Scholar 

  133. Cazzola M, Lobefalo G, Lupis F, et al. The effects of cefonicid on the pharmacokinetics of a once a day theophylline formulation. Int J Clin Pharmacol Res 1989; 9: 169–73

    PubMed  CAS  Google Scholar 

  134. Parent M, St.-Laurent M, Le Bel M. Safety of fleroxacin coadministered with theophylline to young and elderly volunteers. Antimicrob Agents Chemother 1990; 34: 1249–53

    Article  PubMed  CAS  Google Scholar 

  135. Robson RA, Begg EJ, Atkinson HC, et al. Comparative effects of ciprofloxacin and lomefloxacin on the oxidative metabolism of theophylline. Br J Clin Pharmacol 1990; 29: 491–3

    Article  PubMed  CAS  Google Scholar 

  136. Nix DE, Norman A, Schentag JJ. Effect of lomefloxacin on theophylline pharmacokinetics. Antimicrob Agents Chemother 1989; 33: 1006–8

    Article  PubMed  CAS  Google Scholar 

  137. Staib AH, Harder S, Fuhr M, et al. Interaction of quinolones with the theophylline metabolism in man: investigations with lomefloxacin and pipemidic acid. Int J Clin Pharmacol Ther Toxicol 1989; 27: 289–93

    PubMed  CAS  Google Scholar 

  138. Wijnands WJA, Cornel JH, Martea M, et al. The effect of multiple-dose oral lomefloxacin on theophylline metabolism in man. Chest 1990; 98: 1440–4

    Article  PubMed  CAS  Google Scholar 

  139. Wijnands WJA, Vree TB, Baars AM, et al. Der Einfluβ der Chinolonderivate auf die Theophyllin Clearance. Fortschr Antimikrob Antineoplast Chemother 1987; 6-10: 2089–96

    Google Scholar 

  140. Sano M, Kawakatsu K, Ohkita C, et al. Effects of enoxacin, ofloxacin and norfloxacin on theophylline disposition in humans. Eur J Clin Pharmacol 1988; 35: 161–5

    Article  PubMed  CAS  Google Scholar 

  141. Fourtillan JB, Granier J, Saint-Salvi B, et al. Pharmacokinetics of ofloxacin and theophylline alone and in combination. Infection 1986; 14 Suppl. 1: S67–9

    Article  PubMed  CAS  Google Scholar 

  142. Cesana M, Brocalli G, Imbimbo BP, et al. Effect of single doses of rufloxacin on the disposition of theophylline and caffeine after single administration. Int J Clin Pharmacol Ther Toxicol 1991; 29: 133–8

    PubMed  CAS  Google Scholar 

  143. Shimada J, Nogita T, Ishibashi Y. Clinical pharmacokinetics of sparfloxacin. Clin Pharmacokinet 1993; 25: 358–69

    Article  PubMed  CAS  Google Scholar 

  144. Dudley MN. A review of the pharmacokinetic profile of temafloxacin. J Antimicrob Chemother 1991; 28 Suppl. C: 55–64

    PubMed  CAS  Google Scholar 

  145. Ruff F, Santais MC, Callens E, et al. Effect of temafloxacin on the pharmacokinetics of theophylline. Am J Med 1991; 91 Suppl. 6A: 76S–80S

    Article  PubMed  CAS  Google Scholar 

  146. Sörgel F, Mahr G, Granneman GR, et al. Effects of 2 quinolone antibacterials, temafloxacin, and enoxacin, on theophylline pharmacokinetics. Clin Pharmacokinet 1992; 22 Suppl. 1: 65–74

    Article  PubMed  Google Scholar 

  147. Ruff F, Santais MC, Chastagnol D, et al. Macrolide et théophylline: absence d’ interaction josamycine-théophylline. Nouv Presse Med 1981; 10: 175

    PubMed  CAS  Google Scholar 

  148. Brazier JL, Kofman J, Faucon G, et al. Retard d’élemination de la théophylline du à la troléandomycine: absence d’ effet de la josamycine. Therapie 1980; 35: 545–9

    PubMed  CAS  Google Scholar 

  149. Lavarenne J, Paire M, Talon O. Influence d’ un nouveau macrolide, la midécamycine, sur les taux sanguins de théophylline. Therapie 1981; 36: 451–6

    PubMed  CAS  Google Scholar 

  150. Principi N, Onorato J, Giuliani MG, et al. Effect of miocamycin on theophylline kinetics in children. Eur J Clin Pharmacol 1987; 31: 701–4

    Article  PubMed  CAS  Google Scholar 

  151. Couet W, Ingrand I, Reigner B, et al. Lack of effect of ponsinomycin on the plasma pharmacokinetics of theophylline. Eur J Clin Pharmacol 1989; 37: 101–4

    PubMed  CAS  Google Scholar 

  152. Debruyne D, Jehan A, Bigot MC, et al. Spiramycin has no effect on serum theophylline in asthmatic patients. Eur J Clin Pharmacol 1986; 30: 505–7

    Article  PubMed  CAS  Google Scholar 

  153. Halawa B. Interakcje teofiliny z erytromycyna ryfampicyna i linkomycina. Pol Tyg Lek 1988; 43: 8.54–7

    Google Scholar 

  154. Reitberg DP, Klarnet JP, Carlson JK, et al. Effect of metronidazole on theophylline pharmacokinetics. Clin Pharmacol 1983; 2: 441–4

    CAS  Google Scholar 

  155. Jonkman JHG, van der Boon WJV, Balant LP, et al. Lack of effect of amoxicillin on theophylline pharmacokinetics. Br J Clin Pharmacol 1985; 19: 99–101

    Article  PubMed  CAS  Google Scholar 

  156. Kadlec GJ, Ha LT, Jarboe CH, et al. Effect of ampicillin on theophylline half-life in infants and young children. South Med J 1978; 71: 1584–5

    Article  PubMed  CAS  Google Scholar 

  157. Mater MG, Cazzola M, Lampa E, et al. Clinical pharmacokinetics of theophylline during co-treatment with ticarcillin plus clavulanic acid in patients suffering from acute exacerbation of chronic bronchitis. J Chemother 1993; 5: 233–6

    Google Scholar 

  158. Jonkman JHG, van der Boon WJV, Schoenmaker R, et al. Lack of influence of co-trimoxazole on theophylline pharmacokinetics. J Pharm Sci 1985; 74: 1103–4

    Article  PubMed  CAS  Google Scholar 

  159. Jonkman JHG, van der Boon WJV, Schoenmaker R. No influence of doxycycline on theophylline pharmacokinetics. Ther Drug Monit 1985; 7: 92–4

    Article  PubMed  CAS  Google Scholar 

  160. Seegev JS, Shefi M, Schey G, et al. Serum theophylline concentrations are not affected by coadministration of doxycycline. Ann Allergy 1986; 56: 156–7

    Google Scholar 

  161. Serti K, Rameis H, Meryn S. Pirenzepine does not alter the pharmacokinetics of theophylline. Int J Clin Pharmacol Ther Toxicol 1987; 25: 15–7

    Google Scholar 

  162. Kamali F, Edwards C, Rawlins MD. Lack of effect of flosequinan on the pharmacokinetics of theophylline. Br J Clin Pharmacol 1991; 32: 124–6

    Article  PubMed  CAS  Google Scholar 

  163. Nielsen-Kudsk JE, Nielsen CB, Mellemkjaer S, et al. Lack of effect of pinacidil on theophylline pharmacokinetics and metabolism in man. Pharmacol Toxicol 1990; 67: 156–8

    Article  PubMed  CAS  Google Scholar 

  164. Heusner JJ, Dukes GE, Rollins DE, et al. Effect of chronically administered ketoconazole on the elimination of theophylline in man. Drug Intell Clin Pharm 1987; 21: 514–7

    PubMed  CAS  Google Scholar 

  165. Daigneault EA, Hamdy RC, Ferslew KE, et al. Investigation of the influence of acetylsalicylic acid on the steady state of long-term therapy with theophylline in elderly male patients with normal renal function. J Clin Pharmacol 1994; 34: 86–90

    PubMed  CAS  Google Scholar 

  166. Maponga C, Barlow JC, Schentag JJ. Lack of effect of piroxicam on theophylline clearance in healthy volunteers. DICP Ann Pharmacother 1990; 24: 123–6

    CAS  Google Scholar 

  167. Kawakatsu K, Kino T, Yasuba H, et al. Effect of ozagrel (OKY-046), a thromboxane synthetase inhibitor, on theophylline pharmacokinetics in asthmatic patients. Int J Clin Pharmacol Ther Toxicol 1990; 28: 158–63

    PubMed  CAS  Google Scholar 

  168. Cerasa LA, Bertino Jr JS, Ludwig EA, et al. Lack of effect of atenolol on the pharmacokinetics of theophylline. Br J Clin Pharmacol 1988; 26: 800–2

    Article  PubMed  CAS  Google Scholar 

  169. Corsi ChM, Nafziger AN, Pieper JA, et al. JS. Lack of effect of atenolol and nadolol on the metabolism of theophylline. Br J Clin Pharmacol 1990; 29: 265–8

    Article  PubMed  CAS  Google Scholar 

  170. Conrad KA, Nyman DW. Effects of metoprolol and propranolol on theophylline elimination. Clin Pharmacol Ther 1980; 28: 463–7

    Article  PubMed  CAS  Google Scholar 

  171. Anderson JL, Ayres JW, Hall CA. Potential pharmacokinetic interaction between theophylline and prednisone. Clin Pharm 1984; 3: 187–8

    PubMed  CAS  Google Scholar 

  172. Fergusson RJ, Scott CM, Rafferty P, et al. Effect of prednisolone on theophylline pharmacokinetics in patients with chronic airflow obstruction. Thorax 1987; 42: 195–8

    Article  PubMed  CAS  Google Scholar 

  173. Jähnicke UA, Krüdewagen B, Schulz A, et al. Absence of a clinically significant interaction between theophylline and furosemide. Eur J Clin Pharmacol 1987; 33: 487–91

    Article  Google Scholar 

  174. Secor JW, Speeg Jr KV, Meredith CG. Lack of effect of nizatidine on hepatic drug metabolism in man. Br J Clin Pharmacol 1985; 20: 710–3

    Article  PubMed  CAS  Google Scholar 

  175. Dal Negro R, Pomari C, Zoccatelli O, et al. Pharmacokinetics of theophylline and the H2-antagonist drugs cimetidine and ranitidine. Int J Clin Pharmacol Ther Toxicol 1984; 22: 221–6

    Google Scholar 

  176. Kelly HW, Powell JR, Donohue JF. Ranitidine at very large doses not inhibit theophylline elimination. Clin Pharmacol Ther 1986; 39: 577–81

    Article  PubMed  CAS  Google Scholar 

  177. Wilson CG, Washington N, Greaves JL, et al. Effect of pretreatment with ranitidine on the pharmacokinetics and gastrointestinal transit of a sustained release theophylline preparation. Arzneimittelforschung 1991; 41: 1154–9

    PubMed  CAS  Google Scholar 

  178. Yoshimura N, Takeuchi H, Ogata H, et al. Effects of roxatidine acetate hydrochloride and cimetidine on the pharmacokinetics of theophylline in healthy subjects. Int J Clin Pharmacol Ther Toxicol 1989; 27: 308–12

    PubMed  CAS  Google Scholar 

  179. Siegmund W, Scheuch E, Zschiesche M, et al. Potential pharmacokinetic interactions of nocloprost clathrate with retarded theophylline and enteric coated diclofenac after single and repeated premedication in healthy volunteers. Int J Clin Pharmacol Ther Toxicol 1993; 31: 407–14

    PubMed  CAS  Google Scholar 

  180. Bachmann KA, Schwartz J, Jauregui L. Predicting the ciprofloxacin-theophylline interaction from single plasma theophylline measurements. Br J Clin Pharmacol 1988; 26: 191–4

    Article  PubMed  CAS  Google Scholar 

  181. De Lauture D, Rey E, D’Athis P, et al. Pharmacokinetic interactions between theophylline and rioprostil. Scand J Gastroenterol 1989; 24 Suppl. 164: 63–7

    Article  Google Scholar 

  182. Fraschini F, Scaglione F, Maierna G, et al. Ribavirin influence on theophylline plasma levels in adult and children. Int J Clin Pharmacol Ther Toxicol 1988; 26: 30–2

    PubMed  CAS  Google Scholar 

  183. Israel BC, Blouin RA, McIntyre W, et al. Effects of interferon-α monotherapy on drug metabolism in cancer patients. Br J Clin Pharmacol 1993; 36: 229–35

    Article  PubMed  CAS  Google Scholar 

  184. Jonkman JHG, Nicholson KG, Farrow PR, et al. Effects of α-interferon on theophylline pharmacokinetics and metabolism. Br J Clin Pharmacol 1989; 27: 795–802

    Article  PubMed  CAS  Google Scholar 

  185. Jonkman JHG, Sollie FAE, Sauter R, et al. The influence of caffeine on the steady-state pharmacokinetics of theophylline. Clin Pharmacol Ther 1991; 49: 248–55

    Article  PubMed  CAS  Google Scholar 

  186. Sato J, Nakata H, Owada E, et al. Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects. Eur J Clin Pharmacol 1993; 44: 295–8

    Article  PubMed  CAS  Google Scholar 

  187. Adebayo GI, Coker HAB. Cimetidine inhibition of adult age and the time course. Biopharm Drug Dispos 1987; 8: 149–53

    Article  PubMed  CAS  Google Scholar 

  188. Adebayo GI, Mabadeje AFB. Theophylline disposition-effects of cimetidine, mebendazole and albendazole. Aliment Pharmacol Ther 1987; 2: 341–6

    Article  Google Scholar 

  189. Cusack BJ, Dawson GW, Mercer GD, et al. Cigarette smoking and theophylline metabolism: effects of cimetidine. Clin Pharmacol Ther 1985; 37: 330–6

    Article  PubMed  CAS  Google Scholar 

  190. Davis RL, Quenzer RW, Kelly HW, et al. Effect of the addition of ciprofloxacin on theophylline pharmacokinetics in subjects inhibited by cimetidine. Ann Pharmacother 1992; 26: 11–3

    PubMed  CAS  Google Scholar 

  191. Grygiel JJ, Miners JO, Drew R, et al. Differential effects of cimetidine on theophylline metabolic pathways. Eur J Clin Pharmacol 1984; 26: 335–40

    Article  PubMed  CAS  Google Scholar 

  192. Lin JH, Chremos AN, Chiou R, et al. Comparative effect of famotidine and cimetidine on the pharmacokinetics of theophylline in normal volunteers. Br J Clin Pharmacol 1987; 24: 669–72

    Article  PubMed  CAS  Google Scholar 

  193. Loi CM, Parker BM, Cusack BJ, et al. Individual and combined effects of cimetidine and ciprofloxacin on theophylline metabolism in male nonsmokers. Br J Clin Pharmacol 1993; 36: 195–200

    Article  PubMed  CAS  Google Scholar 

  194. Adebayo GI, Mabadeje AF. Effect of nifedipine on antipyrine and theophylline disposition. Biopharm Drug Dispos 1990; 11: 157–64

    Article  PubMed  CAS  Google Scholar 

  195. Vestal RE, Thummel KE, Musser B, et al. Cimetidine inhibits theophylline clearance in patients with chronic obstructive pulmonary disease: a study using stable isotope methodology during multiple oral dose administration. Br J Clin Pharmacol 1983; 15: 411–8

    Article  PubMed  CAS  Google Scholar 

  196. Prince RA, Casabar E, Adair CG, et al. Effects of quinolone antimicrobials on theophylline pharmacokinetics. J Clin Pharmacol 1989; 29: 650–4

    PubMed  CAS  Google Scholar 

  197. Wijnands WJA, Vree TB, van Herwaarden CLA. The influence of quinolone derivatives on theophylline clearance. Br J Clin Pharmacol 1986; 22: 677–83

    Article  PubMed  CAS  Google Scholar 

  198. Loi CM, Day JD, Jue SG, et al. Dose-dependent inhibition of theophylline metabolism by disulfiram in recovering alcoholics. Clin Pharmacol Ther 1989; 45: 476–86

    Article  PubMed  CAS  Google Scholar 

  199. Rogge MC, Solomon WR, Sedman AJ, et al. The theophyllineenoxacin interaction: I. Effect of enoxacin dose size on theophylline disposition. Clin Pharmacol Ther 1988; 44: 579–87

    Article  PubMed  CAS  Google Scholar 

  200. Rogge MC, Solomon WR, Sedman AJ, et al. The theophylline-enoxacin interaction. II. Changes in the disposition of theophylline and its metabolites during intermittent administration of enoxacin. Clin Pharmacol Ther 1989; 46: 420–8

    Article  PubMed  CAS  Google Scholar 

  201. Wijnands WJA, Vree TB, van Herwaarden CLA. Enoxacin decreases the clearance of theophylline in man. Br J Clin Pharmacol 1985; 20: 583–8

    Article  PubMed  CAS  Google Scholar 

  202. Branigan TA, Robbins RA, Cady WJ, et al. The effect of erythromycin on the absorption and disposition kinetics of theophylline. Eur J Clin Pharmacol 1981; 21: 115–20

    Article  PubMed  CAS  Google Scholar 

  203. Prince RA, Wing DS, Weinberger M, et al. Effect of erythromycin on theophylline kinetics. J Allergy Clin Immunol 1981; 68: 427–31

    Article  PubMed  CAS  Google Scholar 

  204. Renton KW, Gray JD, Hung OR. Depression of theophylline elimination by erythromycin. Clin Pharmacol Ther 1981; 30: 422–6

    Article  PubMed  CAS  Google Scholar 

  205. Huang SM, Weintraub HS, Marriott TB, et al. Etintidinetheophylline interaction study in humans. Biopharm Drug Dispos 1987; 8: 561–9

    Article  PubMed  CAS  Google Scholar 

  206. Höglund P, Nilsson LG, Paulsen O. Interaction between isoniazid and theophylline. Eur J Respir Dis 1987; 70: 110–6

    PubMed  Google Scholar 

  207. Samigun, Mulyono, Sanioso B. Lowering of theophylline clearance by isoniazid in slow and rapid acetylators. Br J Clin Pharmacol 1990; 29: 570–3

    Article  PubMed  CAS  Google Scholar 

  208. Hurwitz A, Vacek JL, Botteron GW, et al. Mexiletine effects on theophylline disposition. Clin Pharmacol Ther 1991; 50: 299–307

    Article  PubMed  CAS  Google Scholar 

  209. Loi CM, Wei X, Vestal RE. Inhibition of theophylline metabolism by mexiletine in young male and female nonsmokers. Clin Pharmacol Ther 1991; 49: 571–80

    Article  PubMed  CAS  Google Scholar 

  210. Stoysich AM, Mohiuddin SM, Destache CJ, et al. Influence of mexiletine on the pharmacokinetics of theophylline in healthy volunteers. J Clin Pharmacol 1991; 31: 354–7

    PubMed  CAS  Google Scholar 

  211. Ueno K, Miyai K, Kato M, et al. Mechanism of interaction between theophylline and mexiletine. DICP Ann Pharmacother 1991; 25: 727–30

    CAS  Google Scholar 

  212. Ho G, Tierney MG, Dales RE. Evaluation of the effect of norfloxacin on the pharmacokinetics of theophylline. Clin Pharmacol Ther 1988; 44: 35–8

    Article  PubMed  CAS  Google Scholar 

  213. Bano G, Raina RK, Zutshi U, et al. Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers. Eur J Clin Pharmacol 1991; 41: 615–7

    Article  PubMed  CAS  Google Scholar 

  214. Miners JO, Wing LMH, Lillywhite KJ, et al. Selectivity and dose-dependency of the inhibitory effect of propanolol on theophylline metabolism in man. Br J Clin Pharmacol 1985; 20: 219–23

    Article  PubMed  CAS  Google Scholar 

  215. Saint-Salvi B, Tremblay D, Surjus A, et al. A study of the interaction of roxithromycin with theophylline and carbamazepine. J Antimicrob Chemother 1987; 20 Suppl. B: 121–9

    PubMed  CAS  Google Scholar 

  216. Colli A, Buccino G, Cocciolo M, et al. Ticlopidine — theophylline interaction. Clin Pharmacol Ther 1987; 41: 358–62

    Article  PubMed  CAS  Google Scholar 

  217. Loi CM, Wei X, Parker BM, et al. The effect of tocainide on theophylline metabolism. Br J Clin Pharmacol 1993; 35: 437–40

    Article  PubMed  CAS  Google Scholar 

  218. Kamada AK, Hill MR, Brenner AM, et al. Effect of low-dose troleandomycin on theophylline clearance: implications for therapeutic drug monitoring. Pharmacotherapy 1992; 12: 98–102

    PubMed  CAS  Google Scholar 

  219. Grygiel JJ, Wing LMH, Farkas J, et al. Effects of allopurinol on theophylline metabolism and clearance. Clin Pharmacol Ther 1979; 26: 660–7

    PubMed  CAS  Google Scholar 

  220. Vozeh S, Powell JR, Cupit GC, et al. Influence of allopurinol on theophylline disposition in adults. Clin Pharmacol Ther 1980; 27: 194–7

    Article  PubMed  CAS  Google Scholar 

  221. Gaska JA, Tietze KJ, Rocci Jr ML, et al. Theophylline pharmacokinetics: Effect of continuous versus intermittent cimetidine IV infusion. J Clin Pharmacol 1991; 31: 668–72

    PubMed  CAS  Google Scholar 

  222. Abernethy DR, Egan JM, Dickinson TH, et al. Substrate-selective inhibition by verapamil and diltiazem: differential disposition of antipyrine and theophylline in humans. J Pharmacol Exper Ther 1988; 244: 994–9

    CAS  Google Scholar 

  223. Christopher MA, Harman E, Hendeles L. Clinical relevance of the interaction of theophylline with diltiazem or nifedipine. Chest 1989; 95: 309–13

    Article  PubMed  CAS  Google Scholar 

  224. Nafziger AN, May JJ, Bertino Jr JS. Inhibition of theophylline elimination by diltiazem therapy. J Clin Pharmacol 1987; 27: 862–5

    PubMed  CAS  Google Scholar 

  225. Sirmans SM, Pieper JA, Lalonde RL, et al. Effect of calcium channel blockers on theophylline disposition. Clin Pharmacol Ther 1988; 44: 29–34

    Article  PubMed  CAS  Google Scholar 

  226. Smith SR, Haffner CA, Kendall MJ. The influence of nifedipine and diltiazem on serum theophylline concentration-time profiles. J Clin Pharm Ther 1989; 14: 403–8

    Article  PubMed  CAS  Google Scholar 

  227. Thompson PJ. Social nocturnal alcohol consumption and pharmacokinetics of theophylline. Chest 1992; 101: 156–9

    Article  PubMed  CAS  Google Scholar 

  228. Dal Negro R, Pomari C, Turco P. Famotidine and theophylline pharmacokinetics — an unexpected cimetidine-like interaction in patients with chronic obstructive pulmonary disease. Clin Pharmacokinet 1993; 24: 255–8

    Article  Google Scholar 

  229. Garty M, Cohen E, Mazar A, et al. Effect of nifedipine and theophylline in asthma. Clin Pharmacol Ther 1986; 40: 195–8

    Article  PubMed  CAS  Google Scholar 

  230. Robson RA, Miners JO, Birkett DJ. Selective inhibitory effects of nifedipine and verapamil on oxidative metabolism: effects on theophylline. Br J Clin Pharmacol 1988; 25: 397–400

    Article  PubMed  CAS  Google Scholar 

  231. Smith SR, Wiggins J, Stableforth DE, et al. Effect of nifedipine on serum theophylline concentrations and asthma control. Thorax 1987; 42: 794–6

    Article  PubMed  CAS  Google Scholar 

  232. Stringer KA, Mallet J, Clarke M, et al. The effect of three different oral doses of verapamil on the disposition of theophylline. Eur J Clin Pharmacol 1992; 43: 35–8

    Article  PubMed  CAS  Google Scholar 

  233. Meyer FP. Einfluβ hormonaler Kontrazeptiva auf die Kinetik anderer Pharmaka. Z Klin Med 1990; 45: 1239–42

    Google Scholar 

  234. Gardner MJ, Jusko WJ. Effects of oral contraceptives and tobacco use on the metabolic pathways of theophylline. Int J Pharm 1986; 33: 55–64

    Article  CAS  Google Scholar 

  235. Richer C, Mathieu M, Bah H, et al. Theophylline kinetics and ventilatory flow in bronchial asthma and chronic airflow obstructions: influence of erythromycin. Clin Pharmacol Ther 1982; 31: 579–86

    Article  PubMed  CAS  Google Scholar 

  236. Ruff F, Prosper M, Pujet JC. Théophylline et antibiotiques: absence d’interaction avec la josamyvine. Therapie 1984; 39: 1–6

    PubMed  CAS  Google Scholar 

  237. Takagi K, Hasegawa T, Yamaki K, et al. Interaction between theophylline and enoxacin. Int J Clin Pharmacol Ther Toxicol 1988; 26: 288–92

    PubMed  CAS  Google Scholar 

  238. Ohashi K, Sakamoto K, Sudo T, et al. Effects of diltiazem and cimetidine on theophylline oxidative metabolism. J Clin Pharmacol 1993; 33: 1233–7

    PubMed  CAS  Google Scholar 

  239. Verdiani P, Di Carlo S, Baronti A. Famotidine effects on theophylline pharmacokinetics in subjects affected by COPD. Comparison with cimetidine and placebo. Chest 1988; 94: 807–10

    Article  PubMed  CAS  Google Scholar 

  240. Lew G, Murray WE, Lane JR, et al. Theophylline-thiabendazole drug interaction. Clin Pharmacol 1989; 8: 225–7

    CAS  Google Scholar 

  241. Sugar AM, Kearns Jr PJ, Haulk et al. Possible thiabendazoleinduced theophylline toxicity. Am Rev Respir Dis 1980; 122: 501–3

    PubMed  CAS  Google Scholar 

  242. Perault MC, Griesemann E, Bouquet S, et al. A study of the interaction of viloxazine with theophylline. Ther Drug Monit 1989; 11: 520–2

    Article  PubMed  CAS  Google Scholar 

  243. Soto J, Sacristan JA, Alsar MJ. Diltiazem treatment impairs theophylline elimination in patients with bronchospastic airway disease. Ther Drug Monit 1994; 16: 49–52

    Article  PubMed  CAS  Google Scholar 

  244. Luther R, Wichert H, Köhler E, et al. Wechselwirkungen von Theophyllin und Nifedipin. Z Erkrank Atm Org 1990; 174: 97–103

    CAS  Google Scholar 

  245. Abernethy DR, Egan JM, Carrum G. Calcium antagonists inhibit oxidative drug biotransformation [abstract]. Clin Res 1986; 34: 394A

    Google Scholar 

  246. Nielsen-Kudsk JE, Buhl JS, Johannessen AC. Verapamilinduced inhibition of theophylline elimination in healthy humans. Pharmacol Toxicol 1990; 66: 101–3

    Article  PubMed  CAS  Google Scholar 

  247. Gin AS, Stringer KA, Welage LS, et al. The effect of verapamil on the pharmacokinetic disposition of theophylline in cigarette smokers. J Clin Pharmacol 1989; 29: 728–32

    PubMed  CAS  Google Scholar 

  248. Hoensch H. Ethanol as enzyme inducer and inhibitor. Pharmacol Ther 1987; 33: 121–8

    Article  PubMed  CAS  Google Scholar 

  249. Ueno K, Miyai K, Bito K. Interaction between theophylline and minocycline. Jpn J Ther Drug Monit 1991; 7: 140–1

    Google Scholar 

  250. Kawai M, Honda A, Yoshida H, et al. Possible theophyllineminocycline interaction. Ann Pharmacother 1992; 26: 1300–1

    PubMed  CAS  Google Scholar 

  251. Thakahashi J, Kawakatsu K, Sawaoka H. Elevation of serum theophylline levels by ipriflavone in a patient with chronic obstructive pulmonary disease. Eur J Clin Pharmacol 1992; 43: 207–8

    Article  Google Scholar 

  252. Hecht L, Murray WE, Rubinstein S. Theophylline — pyrantel pamoate interaction. Drug Intell Clin Pharm 1989; 23: 258

    CAS  Google Scholar 

  253. Amitai Y, Glustein J, Godfrey S. Enhancement of theophylline clearance by oral albuterol. Chest 1992; 102: 786–9

    Article  PubMed  CAS  Google Scholar 

  254. Lønning PE, Kvinnsland S, Bakke OM. Effect of aminoglutethimide on antipyrine, theophylline, and digitoxin disposition in breast cancer. Clin Pharmacol Ther 1984; 36: 796–802

    Article  PubMed  Google Scholar 

  255. Kappas A, Alvares AP, Anderson KE, et al. Effect of charcoalbroiled beef on antipyrine and theophylline metabolism. Clin Pharmacol Ther 1978; 23: 445–50

    PubMed  CAS  Google Scholar 

  256. Feldman CH, Hutchinson VE, Pippenger CE, et al. Effect of dietary protein and carbohydrate on theophylline metabolism in children. Pediatrics 1980; 66: 956–62

    PubMed  CAS  Google Scholar 

  257. Juan D, Worwag EM, Schoeller DA, et al. Effects of dietary protein on theophylline pharmacokinetics and caffeine and aminopyrine breath tests. Clin Pharmacol Ther 1986; 40: 187–94

    Article  PubMed  CAS  Google Scholar 

  258. Kappas A, Anderson KE, Conney AH, et al. Influence of dietary protein and carbohydrate on antipyrine and theophylline metabolism in man. Clin Pharmacol Ther 1976; 20: 643–53

    PubMed  CAS  Google Scholar 

  259. Hemmstreet MP, Miles MV, Rutland RO. Effect of intravenous isoproterenol on theophylline kinetics. J Allergy Clin Immunol 1982; 69: 360–4

    Article  Google Scholar 

  260. O’Rourke PP, Crone RK. Effect of isoproterenol on measured theophylline levels. Crit Care Med 1984; 12: 373–5

    Article  PubMed  Google Scholar 

  261. Jusko WJ, Schentag JJ, Clark JH, et al. Enhanced biotransformation of theophylline in marihuana and tobacco smokers. Clin Pharmacol Ther 1978; 24: 406–10

    CAS  Google Scholar 

  262. Dahlqvist R, Steiner E, Koike Y, et al. Induction of theophylline metabolism by pentobarbital. Ther Drug Monit 1989; 11: 408–10

    PubMed  CAS  Google Scholar 

  263. Adebayo GI. Interaction between phenytoin and theophylline in healthy volunteers. Clin Exper Pharmacol Physiol 1988; 15: 883–7

    Article  CAS  Google Scholar 

  264. Crowley JJ, Cusack BJ, Jue SG, et al. Cigarette smoking and theophylline metabolism: effects of phenytoin. Clin Pharmacol Ther 1987; 42: 334–40

    Article  PubMed  CAS  Google Scholar 

  265. Crowley JJ, Cusack BJ, Jue SG, et al. Aging and drug interactions. II. Effect of phenytoin and smoking on the oxidation of theophylline and cortisol in healthy men. J Pharmacol Exper Ther 1988; 245: 513–23

    CAS  Google Scholar 

  266. Miller M, Cosgriff J, Kwong T, et al. Influence of phenytoin on theophylline clearance. Clin Pharmacol Ther 1984; 35: 666–9

    Article  PubMed  CAS  Google Scholar 

  267. Adebayo GI, Akintonwa A, Mabadeje AFB. Attenuation of rifampicin-induced theophylline metabolism by diltiazem/rifampicin coadministration in healthy volunteers. Eur J Clin Pharmacol 1989; 37: 127–31

    Article  PubMed  CAS  Google Scholar 

  268. Boyce EG, Dukes GE, Rollins DE, et al. The effect of rifampin on theophylline kinetics. J Clin Pharmacol 1986; 26: 696–9

    PubMed  CAS  Google Scholar 

  269. Powell-Jackson PR, Jamieson AP, Gray BJ, et al. Effect of rifampicin administration on theophylline pharmacokinetics in humans. Am Rev Respir Dis 1985; 131: 939–40

    PubMed  CAS  Google Scholar 

  270. Robson RA, Miners JO, Wing LMH, et al. Theophylline-rifampicin interaction non-selective induction of theophylline metabolic pathways. Br J Clin Pharmacol 1984; 18: 445–8

    Article  PubMed  CAS  Google Scholar 

  271. Straughn AB, Henderson RP, Lieberman PL, et al. Effect of rifampin on theophylline disposition. Ther Drug Monit 1984; 6: 153–6

    Article  PubMed  CAS  Google Scholar 

  272. Birkett DJ, Miners JO, Attwood J. Evidence for a dual action of sulphinpyrazone on drug metabolism in man: theophyllinesulphinpyrazone interaction. Br J Clin Pharmacol 1983; 15: 567–9

    Article  PubMed  CAS  Google Scholar 

  273. Grygiel JJ, Birkett DJ. Cigarette smoking and theophylline clearance and metabolism. Clin Pharmacol Ther 1981; 30: 491–6

    Article  PubMed  CAS  Google Scholar 

  274. Hunt SN, Jusko WJ, Yurchak AM. Effect of smoking on theophylline disposition. Clin Pharmacol Ther 1976; 19: 546–51

    PubMed  CAS  Google Scholar 

  275. Ishizaki T, Horai Y, Sasaki T, et al. Bioavailability and pharmacokinetics of theophylline following plain uncoated and sustained-release dosage forms in relation to smoking habit. II. Multiple dosage study. Eur J Clin Pharmacol 1983; 24: 361–9

    Article  PubMed  CAS  Google Scholar 

  276. Auteri A, Blardi P, Bruni F, et al. Pharmacokinetics and pharmacodynamics of slow-release theophylline during treatment with nimesulide. Int J Clin Pharmacol Res 1992; 11: 211–5

    Google Scholar 

  277. Casto DT, Schnapf BM, Clotz MA. Lack of effect of short-term passive smoking on the metabolic disposition of theophylline. Eur J Clin Pharmacol 1990; 39: 399–402

    Article  PubMed  CAS  Google Scholar 

  278. Matsunga SK, Plezia PM, Karol MD, et al. Effects of passive smoking on theophylline clearance. Clin Pharmacol Ther 1989; 46: 399–407

    Article  PubMed  CAS  Google Scholar 

  279. Landay RA, Gonzales MA, Taylor JC. Effect of phenobarbital on theophylline disposition. J Allergy Clin Immunol 1978; 62: 27–9

    Article  PubMed  CAS  Google Scholar 

  280. Danzinger Y, Garty M, Volwitz B, et al. Reduction of serum theophylline levels by terbutaline in children with asthma. Clin Pharmacol Ther 1985; 37: 469–71

    Article  Google Scholar 

  281. Garty M, Paul-Keslin L, Ilfeld DN, et al. Increased theophylline clearance in asthmatic patients due to terbutaline. Eur J Clin Pharmacol 1989; 36: 25–8

    Article  PubMed  CAS  Google Scholar 

  282. Lombardi TP, Bertino JS, Goldberg A, et al. The effects of a beta-2 selective adrenergic agonist and a beta-nonselective antagonist on theophylline clearance. J Clin Pharmacol 1987; 27: 523–9

    PubMed  CAS  Google Scholar 

  283. Snidow J, Stephens M, Self T, et al. Acute effects of short-term subcutaneous terbutaline on theophylline disposition. Eur J Clin Pharmacol 1987; 32: 191–3

    Article  PubMed  CAS  Google Scholar 

  284. Marquis JF, Carruthers SG, Spenge JD, et al. Phenytoin-theophylline interaction. N Engl J Med 1982; 307: 1189–90

    Article  PubMed  CAS  Google Scholar 

  285. Gibson GA, Blouin RA, Bauer LA, et al. Influence of high-dose pentobarbital on theophylline pharmacokinetics: a case report. Ther Drug Monit 1985; 7: 181–4

    Article  PubMed  CAS  Google Scholar 

  286. Kandrotas RJ, Cranfield TL, Gal P, et al. Effect of phenobarbital administration on theophylline clearance in premature neonates. Ther Drug Monit 1990; 12: 139–43

    Article  PubMed  CAS  Google Scholar 

  287. Piafsky KM, Sitar DS, Ogilvie RI. Effect of phenobarbital on the disposition of intravenous theophylline. Clin Pharmacol Ther 1977; 22: 336–9

    PubMed  CAS  Google Scholar 

  288. Paladino JA, Blumer NA, Maddox RR. Effect of secobarbital on theophylline clearance. Ther Drug Monit 1983; 5: 135–9

    Article  PubMed  CAS  Google Scholar 

  289. Anderson KE, McCleery RB, Vesell ES, et al. Diet and cimetidine induce comparable changes in theophylline metabolism in normal subjects. Hepatology 1991; 13: 941–6

    Article  PubMed  CAS  Google Scholar 

  290. Jusko WJ. Role of tobacco smoking in pharmacokinetics. J Pharmacokinet Biopharm 1978; 6: 7–39

    PubMed  CAS  Google Scholar 

  291. Rice JM, Diwan BA, Hu H, et al. Enhancement of hepatocarcinogenesis and induction of specific cytochrome P450-dependent monoxygenase activities by the barbiturates allobarbital, aprobarbital, pentobarbital, secobarbital and 5-phenyl- and 5-ethylbarbituric acids. Carcinogenesis 1994; 15: 395–402

    Article  PubMed  CAS  Google Scholar 

  292. Weinberger M, Hendeles L. Current concepts. Slow release theophylline rational and basis for product selection. N Engl J Med 1983; 308: 760–4

    Article  PubMed  CAS  Google Scholar 

  293. Wyatt RA. Guidelines for theophylline dosage and serum level monitoring. In: Jonkman JHG, Jenne JW, Simons FER, editors. Current clinical practice, series No 8. Amsterdam: Excerpta Medica, 1984: 189–94

    Google Scholar 

  294. Walther H, Banditt P, Köhler E, et al. Zur Effektivität des pharmakokinetischen Therapieservice. Z Klin Med 1989; 44: 135–40

    Google Scholar 

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  1. Department of Clinical Pharmacology, University of Magdeburg, Magdeburg, Germany

    Uwe Tröger & Frank P. Meyer

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Tröger, U., Meyer, F.P. Influence of Endogenous and Exogenous Effectors on the Pharmacokinetics of Theophylline. Clin. Pharmacokinet. 28, 287–314 (1995). https://doi.org/10.2165/00003088-199528040-00003

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