Skip to main content
Log in

Theophylline Poisoning

Pharmacological Considerations and Clinical Management

  • Toxicology Management Review
  • Published:
Medical Toxicology Aims and scope Submit manuscript

Summary

The recent marketing of slow release preparations of theophylline and new indications for the use of the drug have resulted in a marked increase in the sale of theophylline products. This phenomenon combined with the drug’s highly variable pharmacokinetics has led to an increase in the number of theophylline intoxications.

The morbidity and mortality rates associated with theophylline intoxication are significant. Therefore it is essential that clinicians are aware of the pathophysiology, clinical presentation and treatment of this poisoning. Theophylline intoxication mainly affects the gastrointestinal, cardiovascular and central nervous systems. Signs and symptoms range from mild gastrointestinal upset to serious central nervous system manifestations such as seizures, a symptom often associated with a bad prognosis.

Theophylline serum concentrations are very useful for making decisions regarding treatment. However, their interpretation should take into account several factors such as the age of the patient and the type of intoxication (acute versus chronic).

Prevention of gastrointestinal absorption should be the principal objective of treatment of an oral theophylline poisoning. The repetitive administration of activated charcoal not only prevents theophylline absorption but also increases its rate of elimination. Once absorbed, external methods such as haemodialysis and haemoperfusion can significantly accelerate the elimination of the drug from the body. Finally, the rapid suppression of seizures and cardiac arrhythmias are essential to prevent severe neurological sequelae and death.

Since theophylline intoxication can be potentially life-threatening, its administration should be monitored with regular measurements of the serum theophylline concentration, especially in the very young and the very old.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aderka D, Shavit G, Garfinkel D, Santo M, Gitter S, et al. Lifethreatening theophylline intoxication in a hypothyroid patient. Respiration 44: 77–80, 1983

    PubMed  CAS  Google Scholar 

  • Ahlmen J, Heath A, Herlitz H, Kvist L, Meilstrand T. Treatment of oral theophylline poisoning. Acta Medica Scandinavica 216: 423–426, 1984

    PubMed  CAS  Google Scholar 

  • Amin DN, Henry JA. Propranolol administration in theophylline overdose. Lancet 1: 520–521, 1985

    PubMed  CAS  Google Scholar 

  • Anderson JR, Poklis A, Slavin RG. A fatal case of theophylline intoxication. Archives of Internal Medicine 143: 559–560, 1983

    PubMed  CAS  Google Scholar 

  • Antal EJ, Kramer PA, Mercik SA, Chapron DJ, Lawson IR. Theophylline pharmacokinetics in advanced age. British Journal of Clinical Pharmacology 12: 637–745, 1981

    PubMed  CAS  Google Scholar 

  • Aranda JV, Louridas T, Vittulo BB, Thorn P, Aldridge A, et al. Metabolism of theophylline to caffeine in human fetal liver. Science 206: 1319–1321, 1979

    PubMed  CAS  Google Scholar 

  • Aranda JV, Sitar DS, Parsons WD, Loughnan PM, Neims AH. Pharmacokinetic aspects of theophylline in premature new-borns. New England Journal of Medicine 295: 413–416, 1976

    PubMed  CAS  Google Scholar 

  • Arnold LA, Spurbeck GH, Shelver WH, Henderson WM. Effect of antacid on gastrointestinal absorption of theophylline. American Journal of Hospital Pharmacy 36: 1059–1062, 1979

    PubMed  CAS  Google Scholar 

  • Arwood LL, Dasta JF, Friedman C. Placental transfer of theophylline: two case reports. Pediatrics 63: 844–846, 1979

    PubMed  CAS  Google Scholar 

  • Assael BM, Caccamo ML, Gerna M, Latini R, Mandelli M, et al. Effect of exchange transfusion on elimination of theophylline in premature neonates. Journal of Pediatrics 91: 331–332, 1977

    PubMed  CAS  Google Scholar 

  • Berlinger WG, Spector R, Goldberg MJ, Johnson GF, Quee CK, et al. Enhancement of theophylline clearance by oral activated charcoal. Clinical Pharmacology and Therapeutics 33: 351–354, 1983

    PubMed  CAS  Google Scholar 

  • Biberstein MP, Fiegler MG, Ward DM. Use of 0-blockade and hemoperfusion for acute theophylline poisoning. Western Journal of Medicine 141: 485–490, 1984

    PubMed  CAS  Google Scholar 

  • Bonati M, Latini R, Marra G, Assael BM, Parmi R. Theophylline metabolism during the first month of life and development. Pediatric Research 15: 304–308, 1981

    PubMed  CAS  Google Scholar 

  • Bory C, Baltassat P, Porthault M, Bethenod M, Frederich A, et al. Biotransformation of theophylline to caffeine in premature newborn. Lancet 2: 1204–1205, 1978

    PubMed  CAS  Google Scholar 

  • Boutroy MJ, Verb P, Monin P, Royer RJ, Royer-Marrot MJ. Methylation of theophylline to caffeine in premature infants. Lancet 1: 830, 1979

    PubMed  CAS  Google Scholar 

  • Brady PG, Bayless TM. Methylxanthine induced small intestine secretion. Johns Hopkins Medical Journal 136: 251–253, 1975

    PubMed  CAS  Google Scholar 

  • Breen KJ, Bury R, Desmond PV, Mashford ML, Morphett B, et al. Effects of cimetidine and ranitidine on hepatic drug metabolism. Clinical Pharmacology and Therapeutics 31: 297–300, 1982

    PubMed  CAS  Google Scholar 

  • Brown MJ, Brown DC, Murphy MB. Hypokalemia from beta 2-receptor stimulation by circulating epinephrine. New England Journal of Medicine 309: 1414–1419, 1983

    PubMed  CAS  Google Scholar 

  • Brunet F, Belmin J, Clement B, Dhaiaut JF, Villemant D, et al. Indication de l’hémoperfusion dans le traitement de l’intoxication aigü à la théophylline. Presse Médicale 14: 550, 1985

    CAS  Google Scholar 

  • Buckley BM, Braithwaite RA, Vale JA. Theophylline poisoning. Lancet 1: 618, 1983

    Google Scholar 

  • Burgan HS, Gupta I, Bate CM. Fatal overdose of theophylline simulating pancreatitis. British Medical Journal 284: 939–940, 1982

    PubMed  CAS  Google Scholar 

  • Burkle WS, Gwitdala CJ. Evaluation of‘toxic’ serum theophylline concentrations. American Journal of Hospital Pharmacy 38: 1164–1166, 1981

    PubMed  CAS  Google Scholar 

  • Cathcart-Rake WF, Kyner JL, Azarnoff DL. Metabolic responses to plasma concentrations of theophylline. Clinical Pharmacology and Therapeutics 26 80–95, 1979

    Google Scholar 

  • Chang TMS, Melendez E, Francoeur TE, Eade NR. Albumin-collodion activated charcoal hemoperfusion in the treatment of severe theophylline intoxication in a 3 year old patient. Pediatrics 65: 811–814, 1980

    PubMed  CAS  Google Scholar 

  • Chranowski RA, Niebergall PJ, Mayock RL, Taubin JM, Sugita ET. Kinetics of intravenous theophylline. Clinical Pharmacology and Therapeutics 22: 188–195, 1977

    Google Scholar 

  • Connell JMC, Cook GM, Mclnnes GT. Metabolic consequences of salbutamol poisoning reversed by propranolol. British Medical Journal 285: 779, 1982

    PubMed  CAS  Google Scholar 

  • Conrad KA, Prosnitz EH. Cardiovascular effects of theophylline: partial attenuation by beta-blockade. European Journal of Clinical Pharmacology 21: 109–114, 1981

    PubMed  CAS  Google Scholar 

  • Conradson TB. Cardiovascular effects of two different xanthines in healthy subjects. Studies at rest, during exercise and in combination with a beta-agonist, terbutaline. European Journal of Clinical Pharmacology 27: 319–324, 1984

    PubMed  CAS  Google Scholar 

  • Covelli HD, Knodel AR, Heppner BT. Predisposing factors to apparent theophylline induced seizures. Annals of Allergy 54: 411–415, 1985

    PubMed  CAS  Google Scholar 

  • Creger RJ, Ball WD, Bahntge MF, et al. Dose-dependent theophylline elimination in an adult. Drug Intelligence and Clinical Pharmacy 17: 202–204, 1983

    PubMed  CAS  Google Scholar 

  • Curry SC, Vance MV, Requa R, Armstead R. Cardiovascular effect of toxic concentrations of theophylline in the dog. Annals of Emergency Medicine 14: 547–553, 1985a

    PubMed  CAS  Google Scholar 

  • Curry SC, Vance MV, Requa R, Armstead R. The effects of toxic concentrations of theophylline on oxygen consumption, ventricular work, and acid base balance and plasma catecholamine levels in the dog. Annals of Emergency Medicine 14: 554–561, 1985b

    PubMed  CAS  Google Scholar 

  • Daly W, Bruns F, Snyder SH. Adenosine receptors in the central nervous system: relationship to the central actions of methylxanthines. Life Sciences 28: 2083–2097, 1981

    PubMed  CAS  Google Scholar 

  • Dahlqvist R, Billing B, Miners JO, Birkett DJ. Nonlinear metabolic disposition of theophylline. Therapeutic Drug Monitoring 6: 290–297, 1984

    PubMed  CAS  Google Scholar 

  • Dean LS, Brown JW. Massive theophylline overdose, survival without hemoperfusion. Journal of American Medical Association 249: 3175–3176, 1983

    Google Scholar 

  • Dederich RA, Szefler J, Grun ER. Intrasubject variation in sustained-release theophylline absorption. Journal of Allergy and Clinical Immunology 67: 465–471, 1981

    PubMed  CAS  Google Scholar 

  • Devaux AM, Leluyer B, Corbery F, Pierre G, Ensel P. Intoxication massive par la théophylline chez un enfant: intérêt de l’épuration extra-rénale. Presse Médicale 12: 1988–1999, 1983

    Google Scholar 

  • Dutt AK, De Soyza ND, Au WY, Hargis JL, Tuck RL. The effect of aminophylline on cardiac rhythm in advanced chronic obstructive pulmonary disease: correlation with serum theophylline levels. European Journal of Respiratory Diseases 64: 264–270, 1983

    PubMed  CAS  Google Scholar 

  • Edvinsson L, Fredholm BB. Characterization of adenosine receptors in isolated cerebral arteries of cat. British Journal of Pharmacology 80: 631, 1983

    PubMed  CAS  Google Scholar 

  • Ehlers M, Zaske DE, Sawchuk RJ. Massive theophylline overdose, rapid elimination by charcoal hemoperfusion. Journal of American Medical Association 240: 474–475, 1978

    CAS  Google Scholar 

  • Ellis EF, Koysooko R, Levy G. Pharmacokinetics of theophylline in children with asthma. Pediatrics 58: 542–547, 1976

    PubMed  CAS  Google Scholar 

  • Fagerström PO, Mellstrand T, Swedmyr N. Absorption of theophylline from conventional and sustained-release tablets. International Journal of Clinical Pharmacology, Therapy and Toxicology 19: 131–138, 1981

    Google Scholar 

  • Fleetham JA, Bird CE, Nakatsu K, Wigle RD, Munt PW. Dose-dependency of theophylline clearance and protein binding. Thorax 36: 382–386, 1981

    PubMed  CAS  Google Scholar 

  • Fredholm BB. Cardiovascular and renal actions of methylxanthines. Progress in Clinical and Biological Research 158: 303–330, 1984

    PubMed  CAS  Google Scholar 

  • Fredholm BB, Persson CGA. Xanthine derivatives as adenosine receptor antagonists. European Journal of Pharmacology 81: 673–676, 1982

    PubMed  CAS  Google Scholar 

  • Gal P, Jusko WJ, Yurchak AM, Franklin BA. Theophylline disposition in obesity. Clinical Pharmacology and Therapeutics 23: 438–444, 1978

    PubMed  CAS  Google Scholar 

  • Gardner MJ, Tornatore KM, Jusko WS, Kanarkowski R. Effects of tobacco smoking and oral contraceptive use on theophylline disposition. British Journal of Clinical Pharmacology 16: 271–280, 1983

    PubMed  CAS  Google Scholar 

  • Gaudreault P, Wason S, Lovejoy Jr FH. Acute pediatric theophylline overdose: a summary of 28 cases. Journal of Pediatrics 102: 474–476, 1983

    PubMed  CAS  Google Scholar 

  • Giacoia G, Jusko WJ, Menke J, Koup JR. Theophylline pharmacokinetics in premature infants with apnea. Journal of Pediatrics 89: 829–832, 1976

    PubMed  CAS  Google Scholar 

  • Ginchansky E, Weinberger M. Relationship of theophylline clearance to oral dosage in children with chronic asthma. Journal of Pediatrics 91: 655–660, 1977

    PubMed  CAS  Google Scholar 

  • Green ER, Green AW, Lane R, Slaughter R, Middleton E. Absorption characteristics of sustained release theophylline capsules administered in apple sauce. Journal of Pediatrics 98: 832–834, 1981

    PubMed  CAS  Google Scholar 

  • Greenberg A, Piraino BH, Kroboth PD, Weiss J. Severe theophylline toxicity: role of conservative measures, antiarrhythmic agents and charcoal hemoperfusion. American Journal of Medicine 76: 854–860, 1984

    PubMed  CAS  Google Scholar 

  • Grygiel JJ, Birkett DJ. Effect of age on patterns of theophylline metabolism. Clinical Pharmacology and Therapeutics 28: 456–462, 1980

    PubMed  CAS  Google Scholar 

  • Grygiel JJ, Wing LMH, Farkas J, Birkett OJ. Effects of allopurinol on theophylline metabolism and clearance. Clinical Pharmacology and Therapeutics 26: 660–667, 1979

    PubMed  CAS  Google Scholar 

  • Gundert-Remy U, Hildebrandt R, Hengen N, Weber E. Non-linear elimination processes of theophylline. European Journal of Clinical Pharmacology 24: 71–78, 1983

    PubMed  CAS  Google Scholar 

  • Haddad ZH, Sakari R. Massive accidental theophylline ingestion. Linear first order elimination kinetics in an infant. Annals of Allergy 48: 178–179, 1982

    PubMed  CAS  Google Scholar 

  • Haley TJ. Metabolism and pharmacokinetics of theophylline in human neonates, children and adults. Drug Metabolism Reviews 14: 295–335, 1983

    PubMed  CAS  Google Scholar 

  • Heimann G, Murgescu J, Bergt U. Influence of food intake on bioavailability of theophylline in premature infants. European Journal of Clinical Pharmacology 22: 171–173, 1982

    PubMed  CAS  Google Scholar 

  • Helliwell M, Berry D. Theophylline poisoning in adults. British Medical Journal 2: 1114, 1979

    PubMed  CAS  Google Scholar 

  • Hemstreet MP, Miles MW, Rutland RO. Effect of intravenous isoproterenol on theophylline kinetics. Journal of Allergy and Clinical Immunology 69: 360–364, 1982

    PubMed  CAS  Google Scholar 

  • Hendeles L, Bighley L, Richardson RH, Hepler CD, Carmichael J. Frequent toxicity from i.v. aminophylline infusions in critically ill patients. Drug Intelligence and Clinical Pharmacy 2: 12–18, 1977a

    Google Scholar 

  • Hendeles L, Burkey S, Bighley L, et al. Unpredictability of theophylline saliva measurements in chronic obstructive pulmonary disease. Journal of Allergy and Clinical Immunology 60: 335–338, 1977b

    PubMed  CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Hendeles L, Weinberger M, Bighley L. Absolute bioavailability of oral theophylline. American Journal of Hospital Pharmacy 34: 525–527, 1977b

    PubMed  CAS  Google Scholar 

  • Hendeles L, Weinberger M, Bighley L. Disposition of theophyl-line after a single intravenous infusion of aminophylline. American Journal of Respiratory Diseases 118: 97–103, 1978

    CAS  Google Scholar 

  • Higbee MD, Kumas M, Galaw SP. Stimulation of endogenous catecholamine release by theophylline: a proposed additional mechanism of action for theophylline effects. Journal of Allergy and Clinical Immunology 70: 377–382, 1982

    PubMed  CAS  Google Scholar 

  • Horowitz LN, Spear JF, Moore EN, Rogers R. Effects of aminophylline on the threshold for initiating ventricular fibrillation during respiratory failure. American Journal of Cardiology 35: 376–379, 1975

    PubMed  CAS  Google Scholar 

  • Iliopoulou A, Aldhous ME, Johnston A, Turner P. Pharmacokinetics interaction between theophylline and erythromycin. British Journal of Clinical Pharmacology 14: 495–499, 1982

    PubMed  CAS  Google Scholar 

  • Isaksson B, Linholm B. Blood plasma level of different theophylline derivatives following parenteral, oral and rectal administration. Acta Medica Scandinavica 171: 33–38, 1962

    Google Scholar 

  • Isles A, Spino M, Tabachnik E, Levinson H, Thiessen J, et al. Theophylline disposition in cystic fibrosis. American Review of Respiratory Diseases 127: 417–421, 1983

    CAS  Google Scholar 

  • Jackson JE, Powell JR, Wandell M, Bentley J, Dorr R. Cimetidine decreases theophylline clearance. American Review of Respiratory Diseases 123: 615–617, 1981

    CAS  Google Scholar 

  • Jacobs MH, Senior RM, Kessler G. Clinical experience with theophylline relationships between dosage, serum concentration and toxicity. American Journal of Medical Association 235: 1983–1986, 1976

    CAS  Google Scholar 

  • Jefferys DB, Raper SM, Helliwell M, Berry DJ, Crome P. Haemoperfusion for theophylline overdose. British Medical Journal 280: 1167, 1980

    PubMed  CAS  Google Scholar 

  • Jenne JW, Chick TW, Miller BA, Strickland RD. Apparent theophylline half-life fluctuation during treatment of acute left ventricular failure. American Journal of Hospital Pharmacy 34: 408–409, 1977

    PubMed  CAS  Google Scholar 

  • Jensen MH. Theophylline inhibition of renal and cerebral nucleoside formation. British Journal of Pharmacology 73: 466–469, 1981

    Google Scholar 

  • Jensen MH, Jorgensen S, Nelsen H, Sanchez R, Anderson PK. Is theophylline induced seizures in man caused by inhibition of cerebral 5′-nucleotidase activity? Acta Pharmacologica et Toxicologica 55: 331–334, 1984

    PubMed  CAS  Google Scholar 

  • Jonkman JHG, Vander Boon WJV, Balant LP, Schoenmaker R, Holtkamp A. Chronopharmacokinetics of theophylline after sustained release and intravenous administration to adults. European Journal of Clinical Pharmacology 26: 215–222, 1984

    PubMed  CAS  Google Scholar 

  • Joseph X, Whitehurst VE, Bloom S, Balazs T. Enhancement of cardiotoxic effects of β-adrenergic bronchodilators by aminophylline in experimental animals. Fundamental and Applied Toxicology 1: 443–447, 1981

    PubMed  CAS  Google Scholar 

  • Josephson GW, Kennedy HL, MacKenzie EJ, Gibson G. Cardiac dysrhythmias during the treatment of acute asthma. A comparison of two treatment regimens by a double blind protocol. Chest 78: 429–435, 1980

    PubMed  CAS  Google Scholar 

  • Jung D, Powell JR, Walson P, Perrier D. Effect of dose on phenytoin absorption. Clinical Pharmacology and Therapeutics 28: 479–485, 1980

    PubMed  CAS  Google Scholar 

  • Jusko WJ, Gardner MJ, Mangione A, Schentag JJ, Koup JR, et al. Factors affecting theophylline clearances: age, tobacco, marijuana, cirrhosis, congestive heart failure, obesity, oral contraceptives, benzodiazepines, barbiturates and ethanol. Journal of Pharmaceutical Sciences 68: 1355–1366, 1979

    Google Scholar 

  • Jusko WJ, Schentag JJ, Clark JH, Gardener MJ, Yurchak AM. Enhanced biotransformation of theophylline in marijuana and tobacco smokers. Clinical Pharmacology and Therapeutics 24: 405–410, 1978

    PubMed  CAS  Google Scholar 

  • Kadlec GJ, Jarbol CH, Pollard SJ, Sublett JL. Acute theophylline intoxication. Biphasic first order elimination kinetics in a child. Annals of Allergy 41: 337–339, 1978

    PubMed  CAS  Google Scholar 

  • Kappas A, Anderson KE, Conney AH, Alvares AP. Influence of dietary protein and carbohydrate on antipyrine and theophylline metabolism in man. Clinical Pharmacology and Therapeutics 20: 643–653, 1976

    PubMed  CAS  Google Scholar 

  • Kearny TE, Manoguerra AS, Curtis GP, Ziegler MG. Theophylline toxicity and the beta-adrenergic system. Annals of Internal Medicine 102: 766–769, 1985

    Google Scholar 

  • Keating G, Mitchell EA, Jackson R, Ziegler MG. Trends in sales of drugs for asthma in New Zealand, Australia, and the United Kingdom 1975–1981. British Medical Journal 289: 348–351, 1983

    Google Scholar 

  • Kelly WJW, Parkin WH. Charcoal hemoperfusion treatment of severe theophylline toxicity. Australian and New Zealand Journal of Medicine 15: 75–77, 1985

    PubMed  CAS  Google Scholar 

  • Kossoy AF, Weir MR, Bryow MV. Theophylline toxicity. Pediatrics 72: 746–747, 1983

    PubMed  CAS  Google Scholar 

  • Koysooko R, Ellis EF, Levy G. Relationship between theophyl-line concentration in plasma and saliva of man. Clinical Pharmacology and Therapeutics 15: 454–460, 1974

    PubMed  CAS  Google Scholar 

  • Krishna GG, Zahrowski JJ, Nissenson AR, et al. Hemodialysis for theophylline overdose. Dialysis and Transplantation 12: 40, 1983

    Google Scholar 

  • Kulig K, Bar-Or D, Cantrill SV, Rosen P, Rumack BH. Management of acutely poisoned patients without gastric emptying. Annals of Emergency Medicine 14: 562–567, 1985

    PubMed  CAS  Google Scholar 

  • LaForce CF, Miller MF, Chai H. Effect of erythromycin on theophylline clearance in asthmatic children. Journal of Pediatrics 99: 153–156, 1981

    PubMed  CAS  Google Scholar 

  • Laggner AN, Kaik G, Lenz K, Druml W, Kleinberger G. Treatment of severe poisoning in the slow release theophylline. British Medical Journal 288: 1497, 1984

    PubMed  CAS  Google Scholar 

  • Lalonde RL, Koob RA, McLean WM, Balsys AJ. The effects of cimetidine on theophylline pharmacokinetics at steady state. Chest 83: 221–224, 1983

    PubMed  CAS  Google Scholar 

  • Landay RA, Gonzalez MA, Taylor JC. Effect of phenobarbital on theophylline disposition. Journal of Allergy and Clinical Immunology 62: 27–29, 1978

    PubMed  CAS  Google Scholar 

  • Lawyer C, Aitchison J, Sutton J, Bennett W. Treatment of theophylline neurotoxicity with resin-hemoperfusion. Annals of Internal Medicine 88: 516–517, 1978

    PubMed  CAS  Google Scholar 

  • Lee CS, Marbury TC, Perrin JH, Fuller TJ. Hemodialysis of theophylline in uremic patients. Journal of Clinical Pharmacology 24: 219–226, 1979

    Google Scholar 

  • Lee CS, Peterson JC, Marbury TC. Comparative pharmacokinetics of theophylline in peritoneal dialysis and hemodialysis. Journal of Clinical Pharmacology 23: 274–280, 1983

    PubMed  CAS  Google Scholar 

  • Levy G, Gibson TP, Whitman W, Procknal J. Hemodialysis clearance of theophylline. Journal of the American Medical Association 237: 1466–1467, 1977

    PubMed  CAS  Google Scholar 

  • Levy G, Koysooko R. Pharmacokinetic analysis of the effect of theophylline on pulmonary function in asthmatic children. Journal of Pediatrics 86: 789–793, 1975

    PubMed  CAS  Google Scholar 

  • Levy G, Koysooko R. Renal clearance of theophylline in man. Journal of Clinical Pharmacology 6: 329–332, 1976

    Google Scholar 

  • Lohmann SM, Miech RP. Theophylline metabolism by the rat liver microsomal system. Journal of Pharmacology and Experimental Therapeutics 196: 213–225, 1976

    PubMed  CAS  Google Scholar 

  • Loughnan PM, Sitar DS, Oglivie RI, Eisen A, Fox F, et al. Pharmacokinetic analysis of the disposition of intravenous theophylline in the young children. Journal of Pediatrics 88: 874–879, 1976

    PubMed  CAS  Google Scholar 

  • Maddux MS, Leeds NH, Organek HW, Hasegawa GR, Bauman JL. The effect of erythromycin on theophylline pharmacokinetics at steady state. Chest 81: 563–565, 1982

    PubMed  CAS  Google Scholar 

  • Mahutte CK, True RD, Michiels TM, Berman JM, Light RW. Increased serum theophylline clearance with orally administered activated charcoal. American Review of Respiratory Diseases 128: 820–822, 1983

    CAS  Google Scholar 

  • Manfredi RF, Vesell ES. Inhibition of theophylline metabolism by long-term allopurinol administration. Clinical Pharmacology and Therapeutics 29: 224–229, 1981

    PubMed  CAS  Google Scholar 

  • Mangione A, Imhoff TE, Lee RV, Shum LY, Jusko W. Pharmacokinetics of theophylline in liver disease. Chest 73: 616–622 1978

    PubMed  CAS  Google Scholar 

  • Marquis JF, Carruthers SG, Spence JD, Bromstone YS, Toogood JH. Phenytoin-theophylline interaction. New England Journal of Medicine 307: 1189–1190, 1982

    PubMed  CAS  Google Scholar 

  • Massey KL, Gotz VP, Wayne LR. Dose-dependent kinetics of theophylline in adults with pulmonary diseases. Therapeutic Drug Monitoring 6: 284–289, 1984

    PubMed  CAS  Google Scholar 

  • May DC, Jarkoe CH, Ellenburg DT, Roe EJ, Kariho J. The effects of erythromycin on theophylline elimination in normal males. Journal of Clinical Pharmacology 22: 125–130, 1982

    PubMed  CAS  Google Scholar 

  • Miceli JN, Clay B, Fleischmann LE, Sarnaik AP, Aronow R, et al. Pharmacokinetics of severe theophylline intoxication managed by peritoneal dialysis. Developmental Pharmacology and Therapeutics 1: 16–25, 1980

    PubMed  CAS  Google Scholar 

  • Miners JO, Grygiel JJ, Drew R, Birkett DJ. Interaction between cimetidine and theophylline in smokers and non-smokers. Clinical and Experimental Pharmacology and Physiology 8: 633–634, 1981

    Google Scholar 

  • Mitenko PA, Oglivie RI. Rapidly achieved plasma concentration plateaus, with observations on theophylline kinetics. Clinical Pharmacology and Therapeutics 13: 329–335, 1972

    PubMed  CAS  Google Scholar 

  • Mitenko PA, Oglivie RI. Pharmacokinetics of intravenous theophylline. Clinical Pharmacology and Therapeutics 14: 509–513, 1973

    PubMed  CAS  Google Scholar 

  • Mountain RD, Neff TA. Oral theophylline intoxication: a serious error of patient and physician understanding. Archives of Internal Medicine 144: 724–727, 1984

    PubMed  CAS  Google Scholar 

  • Myhre KI, Walstad RA. The influence of antacid on the absorption of two different sustained-release formulations of theophylline. British Journal of Clinical Pharmacology 15: 683–687, 1981

    Google Scholar 

  • Nassif EG, Weinberger M, Shannon D, Guiang SF, Hendeles L. et al. Theophylline disposition in infancy. Journal of Pediatrics 98: 158–161, 1981

    PubMed  CAS  Google Scholar 

  • Nielsen-Kudsk F, Magnussen I, Jakobsen P. Pharmacokinetics of theophylline in ten elderly patients. Acta Pharmacologica et Toxicologica 42: 226–234, 1978

    PubMed  CAS  Google Scholar 

  • Oberdörster G, Lang R, Zimmer R. Influence of adenosine and lowered cerebral blood flow on the cerebrovascular effects of theophylline. European Journal of Pharmacology 30: 197–204, 1975

    PubMed  Google Scholar 

  • Oglivie RI. Clinical pharmacokinetics of theophylline. Clinical Pharmacokinetics 3: 267–293, 1978

    Google Scholar 

  • Oliw E, Anggard E, Fredholm BB. Effect of indomethacin on the renal actions of theophylline. European Journal of Pharmacology 43: 9–16, 1977

    PubMed  CAS  Google Scholar 

  • Olson KR, Benowitz NL, Woo OF, Pond SM. Theophylline overdose: acute single ingestion versus chronic repeated overme dication. American Journal of Emergency Medicine 3: 386–394, 1985

    PubMed  CAS  Google Scholar 

  • Opie LH, Muller C, Nathan D, Davies P, Lubbe WF. Evidence for role of cyclic AMP as second messenger of arrhythmogenic effects of beta-stimulation. Advances in Cyclic Nucleotide Research 12: 63–69, 1980

    PubMed  CAS  Google Scholar 

  • Park GD, Radomski L, Goldberg MJ, Spector R, Johnson GF, et al. Effects of size and frequency of oral doses of charcoal on theophylline clearance. Clinical Pharmacology and Therapeutics 34: 663–666, 1983a

    PubMed  CAS  Google Scholar 

  • Park GD, Spector R, Roberts R, Goldberg MJ, Weismann D, et al. Emergency Medicine 3: 386–394, 1985 et al. Use of hemoperfusion for treatment of theophylline intoxication. American Journal of Medicine 74: 961–966, 1983b

    PubMed  CAS  Google Scholar 

  • Park GD, Spector R, Goldberg MJ, Johnson GF, Feldman R, et al. Weismann D, et al. Effect of the surface area of activated charcoal on theophylline clearance. Journal of Clinical Pharmacology 24: 289–292, 1984

    PubMed  CAS  Google Scholar 

  • Pedersen S, Moller-Petersen J. Erratic absorption of slow-release theophylline sprinkle product. Pediatrics 74: 534–538, 1984

    PubMed  CAS  Google Scholar 

  • Persson CG, Erjefalt L. Convulsive effect of theophylline in conscious and anaesthetized guinea-pigs. Acta Pharmacologica et Toxicologica 48: 32–38, 1981

    PubMed  CAS  Google Scholar 

  • Persson CG, Erjefalt L. Seizure activity in animals given enprofylline and theophylline, two xanthines with partly different mechanisms of action. Archives Internationales de Pharmacodynamie et de Thérapie 258: 267–282, 1982

    PubMed  CAS  Google Scholar 

  • Phillis JW, Edstrom JP, Kostopoulos GK, Kirkpatrick JR. Effects of adenosine and adenine nucleotides on synaptic transmission in cerebral cortex. Canadian Journal of Physiology and Pharmacology 57: 1289–1312, 1979

    PubMed  CAS  Google Scholar 

  • Phillis JH, Kostopoulos GK. Adenosine as a putative transmitter in the cerebral cortex. Studies with the potentiators and antagonists. Life Sciences 17: 1085–1094, 1975

    CAS  Google Scholar 

  • Piafsky KM, Sitar DS, Rangnore RE, Ogilvie RI. Theophylline kinetics in acute pulmonary edema. Clinical Pharmacology and Therapeutics 21: 310–316, 1977a

    PubMed  CAS  Google Scholar 

  • Piafsky KM, Sitar DS, Rangnore RE, Ogilvie RI. Theophylline disposition in patients with hepatic cirrhosis. New England Journal of Medicine 296: 1495–1497, 1977b

    PubMed  CAS  Google Scholar 

  • Poison Control Statistics, Product Related Disease Division, Bureau of Epidemiology, Health Protection Branch, Ministry of National Health and Welfare, Canada, 1984

  • Pond SM. Role of repeated oral doses of activated charcoal in clinical toxicology. Medical Toxicology 1: 3–11, 1986

    PubMed  CAS  Google Scholar 

  • Powell DW, Farris RK, Carbinetto ST. Theophylline, cyclic AMP, choleragen and electrolyte transport by rabbit ileum. American Journal of Physiology 227: 1428–1435, 1974

    PubMed  CAS  Google Scholar 

  • Powell JR, Rogers JF, Wargin WA, Cross RE, Eshelman FN. The influence of cimetidine vs ranitidine on theophylline pharmacokinetics. (Abstract.) Clinical Pharmacology and Therapeutics 31: 261, 1982

    Google Scholar 

  • Powell JR, Thiercelin JF, Vozeh S, Sansom L, Riegelman S. The influence of cigarette smoking and sex on theophylline disposition. American Review of Respiratory Diseases 116: 17–23, 1977

    CAS  Google Scholar 

  • Prince RA, Wing DS, Weinberger MM, Hendeles LS, Riegelman S. Effect of erythromycin on theophylline kinetics. Journal of Allergy and Clinical Immunology 68: 427–431, 1981

    PubMed  CAS  Google Scholar 

  • Radomski L, Park GD, Goldberg MJ, Spector R, Johnson GF, et al. Model for theophylline overdose treatment with oral activated charcoal. Clinical Pharmacology and Therapeutics 35: 402–408, 1984

    PubMed  CAS  Google Scholar 

  • Reinhardt D, Richter O, Genz T, Fuchs F. Linear elimination kinetics but nonlinear pharmacodynamics in theophylline intoxication in a child. International Journal of Clinical Pharmacology, Therapy and Toxicology 20: 171–173, 1982

    CAS  Google Scholar 

  • Reisz G, Pingleton SK, Melethil S, Ryan PB. The effect of erythromycin on theophylline pharmacokinetics in chronic bronchitis. American Review of Respiratory Diseases 127: 581–584, 1983

    CAS  Google Scholar 

  • Reitberg DP, Bernhard H, Schentag JJ. Alteration of theophylline clearance and half-life by cimetidine in normal volunteers. Annals of Internal Medicine 92: 582–585, 1981

    Google Scholar 

  • Renton KW, Gray JD, Hung OR. Depression of theophylline elimination by erythromycin. Clinical Pharmacology and Therapeutics 30: 422–426, 1981

    PubMed  CAS  Google Scholar 

  • Resar RK, Walson P, Fritz B, Barbee R. Effect of arterial pH on intravenous theophylline loading in chronic obstructive pulmonary disease. (Abstract.) American Review of Respiratory Diseases 115: 155, 1977

    Google Scholar 

  • Richards W, Church JA, Brent DK. Theophylline-associated seizures in children. Annals of Allergy 54: 276–279, 1985

    PubMed  CAS  Google Scholar 

  • Roberts RK, Grice J, McGuffie C, Heilbronn L. Oral contraceptive steroids impair the elimination of theophylline. Journal of Laboratory and Clinical Medicine 101: 821–825, 1983

    PubMed  CAS  Google Scholar 

  • Roberts RK, Grice J, Wood L, Petroff V, McGuffie C. Cimetidine impairs the elimination of theophylline and antipyrine. Gastroenterology 81: 19–21, 1981

    PubMed  CAS  Google Scholar 

  • Robertson NJ. Fatal overdose from a sustained-release theophylline preparation. Annals of Emergency Medicine 14: 115–119, 1985

    Google Scholar 

  • Rogers RJ, Kalisker A, Wiener MB, Szefler SJ. Inconsistent absorption from a sustained-release theophylline preparation during continuous therapy in asthmatic children. Journal of Pediatrics 106: 496–501, 1985

    PubMed  CAS  Google Scholar 

  • Rosen JP, Danish M, Ragni MC, Lopez Saccar C, Yaffe SJ, et al. Theophylline pharmacokinetics in the young infant. Pediatrics 64: 248–251, 1979

    PubMed  CAS  Google Scholar 

  • Russo ME. Management of theophylline intoxication with charcoal-column hemoperfusion. New England Journal of Medicine 300: 24–26, 1979

    PubMed  CAS  Google Scholar 

  • Rutherford JD, Vatner SF, Braunwald E. Effects and mechanism of action of aminophylline on cardiac function and regional blood flow distribution in conscious dogs. Circulation 63: 378–387, 1981

    PubMed  CAS  Google Scholar 

  • Sahney S, Abarzna J, Sessum L. Hemoperfusion in theophylline neurotoxicity. Pediatrics 71: 615–619, 1983

    PubMed  CAS  Google Scholar 

  • Sarrazin E, Hendeles L, Weinberger M, Muir K, Riegelman S. Dose-dependent kinetics for theophylline. Observations among ambulatory asthmatic children. Journal of Pediatrics 97: 825–828, 1980

    CAS  Google Scholar 

  • Schack JA, Waxier SH. An ultra violet spectrophotometric method for the determination of theophylline and theobromine in blood and tissues. Journal of Pharmacology and Experimental Therapeutics 97: 283–291, 1949

    PubMed  CAS  Google Scholar 

  • Scher S, Shim C, Williams MH. Effect of bronchodilator agents on arrhythmia. (Abstract.) American Review of Respiratory Diseases 111: 897, 1976

    Google Scholar 

  • Schwertner HA, Ludden TM, Wallace JE. Determination of theophylline in plasma by electron capture gas chromatography. Analytical Chemistry 48: 1875–1878, 1976

    PubMed  CAS  Google Scholar 

  • Sessler CN, Glauser FL, Cooper KR. Treatment of theophylline toxicity with oral activated charcoal. Chest 87: 325–329, 1985

    PubMed  CAS  Google Scholar 

  • Shaw LM, Fields L, Mayack R. Factors influencing theophylline serum protein binding. Clinical Pharmacology and Therapeutics 32: 490–496, 1982

    PubMed  CAS  Google Scholar 

  • Simons FER, Simons KJ. Pharmacokinetics of theophylline in infancy. Journal of Clinical Pharmacology 18: 472–476, 1978

    PubMed  CAS  Google Scholar 

  • Simons KJ, Simons FER, Briggs CJ, Lo L. Theophylline protein binding in humans. Journal of Pharmaceutical Sciences 68: 252–253, 1979

    PubMed  CAS  Google Scholar 

  • Sintek KC, Hendeles L, Weinberger M. Inhibition of theophylline absorption by activated charcoal. Journal of Pediatrics 94: 314–316, 1979

    PubMed  CAS  Google Scholar 

  • Soldin SJ, Hill JG. A rapid micromethod for measuring theophylline in serum by reverse phase high-performance liquid chromatography. Clinical Biochemistry 10: 74–77, 1977

    PubMed  CAS  Google Scholar 

  • Somani SM, Khanna NN, Bada HS. Caffeine and theophylline: serum/CSF correlation in premature infants. Journal of Pediatrics 96: 1091–1093, 1980

    PubMed  CAS  Google Scholar 

  • Staib AH, Schuppan D, Lissner R, Zilly W, Bomhard GV, et al. Pharmacokinetics and metabolism of theophylline in patients with liver diseases. Interational Journal of Clinical Pharmacology, Therapy and Toxicology 18: 500–502, 1980

    CAS  Google Scholar 

  • Stec GP, Greenberg P, Ruo TS, Henthorn T, Morita Y, et al. Kinetics of theophylline transfer to breast milk. Clinical Pharmacology and Therapeutics 28: 404–408, 1980

    PubMed  CAS  Google Scholar 

  • Stone WE, Javid MJ. Aminophylline and imidazole as convulsants. Archives Internationales de Pharmacodynamie et de Thérapie 248: 120–131, 1980

    PubMed  CAS  Google Scholar 

  • Strubelt O. The influence of reserpine, propranolol and adrenal medullectomy on the hyperglycemia action of theophylline and caffeine. Archives Internationales de Pharmacodynamie et de Thérapie 179: 214–224, 1969

    Google Scholar 

  • Tang-Liu DDS, Riegelman S. Metabolism of theophylline to caffeine in adults. Research Communications in Chemical Pathology and Pharmacology 34: 371–380, 1981

    PubMed  CAS  Google Scholar 

  • Tang-Liu DDS, Williams RL, Riegelman S. Nonlinear theophylline elimination. Clinical Pharmacology and Therapeutics 31: 358–369, 1982

    PubMed  CAS  Google Scholar 

  • Thomas EK, Manoguerra AS, Curtis GP. Theophylline toxicity and the beta-adrenergic system. Annals of Internal Medicine 102: 766–769, 1985

    Google Scholar 

  • Thompson RD, Nagasawa HT, Jenne JW. Determination of theophylline and its metabolites in human urine and serum by high pressure liquid chromatography. Journal of Laboratory and Clinical Medicine 84: 584–593, 1974

    PubMed  CAS  Google Scholar 

  • Tornatore KM, Kanarkowski R, McCarthy TL, Gardner MJ, Yurchak AM, et al. Effect of chronic oral contraceptive steroids on theophylline disposition. European Journal of Clinical Pharmacology 23: 129–134, 1982

    PubMed  CAS  Google Scholar 

  • True RJ, Berman JM, Mahutte CK. Treatment of theophylline toxicity with oral activated charcoal. Critical Care Medicine 12: 113–114, 1984

    PubMed  CAS  Google Scholar 

  • Truitt EB, McKusick VA, Krantz JC. Theophylline blood levels after oral, rectal and intravenous administration and correlation with diuretic action. Journal of Pharmacology and Experimental Therapeutics 100: 309–315, 1950

    PubMed  CAS  Google Scholar 

  • Tserng K, King KC, Takieddine FN. Theophylline metabolism in premature infants. Clinical Pharmacology and Therapeutics 29: 594–600, 1981

    PubMed  CAS  Google Scholar 

  • Upton RA, Thiercelin JF, Guentert TW, Wallace SM, Powell JR, et al. Intraindividual variability in theophylline pharmacokinetics: statistical verification in 39 of 60 healthy young adults. Journal of Pharmacokinetics and Biopharmaceutics 10: 123–124, 1982

    PubMed  CAS  Google Scholar 

  • Utama I, Kreukniet J, Meeting PG, Maes Raa, Pharmacokinetics and pharmacodynamics of a short and long-acting theophylline medication (Theolair and Theolair retard) in normals and asthmatics. I. Pharmacokinetics. International Journal of Clinical Pharmacology, Therapy and Toxicology 21: 287–291, 1983

    CAS  Google Scholar 

  • Valet SB, Schwartz RH, Brooks JG. Pharmacokinetics of theophylline and bioavailability of a sustained release theophylline preparation in patients with cystic fibrosis. Annals of Allergy 50: 161–165, 1983

    PubMed  CAS  Google Scholar 

  • Vallner JJ, Speir WA, Kolbeck RC, Harrison GN, Bransome ED. Effect of pH on the binding of theophylline to serum protein. American Review of Respiratory Diseases 120: 83–86, 1979

    CAS  Google Scholar 

  • Vaucher Y, Lightner ES, Walson PD. Theophylline poisoning. Journal of Pediatrics 90: 827–830, 1977

    PubMed  CAS  Google Scholar 

  • Vestal RE, Eiriksson CE, Musser B, Ozaki LK, Halter JB. Effect of intravenous aminophylline on plasma levels of catechol-amines and related cardiovascular and metabolic responses in man. Circulation 67: 162–171, 1983

    PubMed  CAS  Google Scholar 

  • Vincent FM. Case report, fatal theophylline-induced seizures. Postgraduate Medicine 63: 76–77, 1978

    PubMed  CAS  Google Scholar 

  • Viouna N, McNay JL, Ludden TM, Schwertner H. Impaired theophylline clearance in patients with cor pulmonale. British Journal of Clinical Pharmacology 7: 33–37, 1979

    Google Scholar 

  • Vozeh S, Powell JR, Cupit GC, Riegelman S, Sheiner LB. Influence of allopurinol on theophylline disposition in adults. Clinical Pharmacology and Therapeutics 27: 194–197, 1980

    PubMed  CAS  Google Scholar 

  • Walker JE. Aminophylline seizures in the rat. Journal of Pharmacy and Pharmacology 33: 479–480, 1981

    PubMed  CAS  Google Scholar 

  • Watanabe H, Nakano S, Nagai K, Ogawa N. Time-dependent absorption of theophylline in man. Journal of Clinical Pharmacology 24: 509–514, 1984

    PubMed  CAS  Google Scholar 

  • Weinberger M. Theophylline poisoning. Pediatrics 73: 878, 1984

    PubMed  CAS  Google Scholar 

  • Weinberger M, Hendeles L. Role of dialysis in the management and prevention of theophylline toxicity. Developmental Pharmacology and therapeutics 1: 26–30, 1980

    PubMed  CAS  Google Scholar 

  • Weinberger M, Hendeles L, Brighley L. The relation of product formulation to absorption of oral theophylline. New England Journal of Medicine 299: 852–857, 1978

    PubMed  CAS  Google Scholar 

  • Weinberger M, Hendeles L, Wong L, Vaughan L. Relationship of formulation and dosing interval to fluctuation of serum theophylline concentration in children with chronic asthma. Journal of Pediatrics 99: 145–152, 1981

    PubMed  CAS  Google Scholar 

  • Weinberger M, Hudgel D, Spector S, Chidsey C. Inhibition of theophylline clearance by troleandomycin. Journal of Allergy and Clinical Immunology 59: 228–231, 1977

    PubMed  CAS  Google Scholar 

  • Welling PG, Lyons LL, Craig WA, Trotchta GA. Influence of diet and fluid on bioavailability of theophylline. Clinical Pharmacology and Therapeutics 17: 475–480, 1975

    PubMed  CAS  Google Scholar 

  • Wells DH, Ferlanto JJ. Survival after massive aminophylline overdose in a premature infant. Pediatrics 64: 252–253, 1979

    PubMed  CAS  Google Scholar 

  • Whyte KF, Addis GJ. Toxicity of salbutamol and theophylline together. Lancet 2: 618–619, 1983

    PubMed  CAS  Google Scholar 

  • Winek CL, Bricker JD, Collom WD, Fochtman FW. Theophylline fatalities. Forensic Science International 15: 233–236, 1980

    PubMed  CAS  Google Scholar 

  • Woo OF, Pond SM, Benowitz NL, Olson KR. Benefit of hemoperfusion in acute theophylline intoxication. Clinical Toxicology 22: 411–424, 1984

    PubMed  CAS  Google Scholar 

  • Woodcock AA, Johnson MA, Geddes DD. Theophylline prescribing, serum concentrations and toxicity. Lancet 2: 610–613, 1983

    PubMed  CAS  Google Scholar 

  • Yarnell PR, Chu NS. Focal scizures and aminophylline. Neurology 25: 819–822, 1975

    PubMed  CAS  Google Scholar 

  • Yeh TF, Pildes RS. Transplacental aminophylline toxicity in a neonate. Lancet 1: 910, 1977

    PubMed  CAS  Google Scholar 

  • Yurchak AM, Jusko WJ. Theophylline secretion into breast milk. Pediatrics 57: 518–520, 1976

    PubMed  CAS  Google Scholar 

  • Zarowitz BJM, Szefler SJ, Lasezkay GM. Effect of erythromycin base on theophylline kinetics. Clinical Pharmacology and Therapeutics 29: 601–605, 1981

    PubMed  CAS  Google Scholar 

  • Zwillich CW, Sutton FD, Neff TA, Cohn WM, Matthay RA, et al. Theophylline-induced seizures in adults. Correlation with serum concentrations. Annals of Internal Medicine 82: 784–787, 1975

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gaudreault, P., Guay, J. Theophylline Poisoning. Medical Toxicology 1, 169–191 (1986). https://doi.org/10.1007/BF03259836

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03259836

Keywords

Navigation