Clinical Pharmacokinetics

, Volume 35, Issue 2, pp 95–134 | Cite as

Pharmacodynamics and Pharmacokinetics of Thiopental

  • Hélène Russo
  • Françoise Bressolle
Review Article Drug Disposition

Abstract

Thiopental is an ultra short-acting barbiturate which remains the standard against which other induction agents are judged; it is also indicated for the therapy of brain hypoxic-ischaemia injuries and status epilepticus. Aspects of drug distribution that govern the onset and end of drug effect have been intensively studied to determine which parameters (in patient characteristics, diseases and administration modalities) influence effective dose and concentrations in individual patients. Thiopental has been used as a reference for pharmacokinetic and/or pharmacodynamic models in the study of rapid and short acting effect drugs. In anaesthesiology the pharmacokinetics of thiopental are described as linear; when doses and duration of treatment increase, nonlinear pharmacokinetics occur because of the saturation and/or the induction of the metabolism.

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References

  1. 1.
    Lundy JS, Towell RM. Annual report for 1934 of the section on anesthesia including data on blood transfusion. Proc Mayo Clin 1935; 10: 257.Google Scholar
  2. 2.
    Breivik H, Safar P, Sands P, et al. Clinical feasibility trials of barbiturate therapy after cardiac arrest. Crit Care Med 1978; 6: 228–44.PubMedCrossRefGoogle Scholar
  3. 3.
    Marshall LF, Smith RW, Shapiro HM. The outcome with aggressive treatment in severe head injuries: Pt II. Acute and chronic barbiturate administration in the management of head injury. J Neurosurg 1979; 50: 26–30.PubMedCrossRefGoogle Scholar
  4. 4.
    Michenfelder JD, Theye RA. Cerebral protection by thiopental during hypoxia. Anesthesiology 1973; 39: 510–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Piatt JH, Schiff SJ. High dose barbiturate therapy in neurosurgery and intensive care. Neurosurgery 1984; 15 (3): 427–42.PubMedCrossRefGoogle Scholar
  6. 6.
    Rockoff MA, Marshall LF, Shapiro HM. High-dose barbiturate therapy in humans: a clinical review of 60 patients. Ann Neurol 1979; 6: 194–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Shapiro HM, Galindo A, Wyte SR, et al. Rapid intraoperative reduction of intracranial pressure with thiopentone. Br J Anaesth 1973; 45: 1057–62.PubMedCrossRefGoogle Scholar
  8. 8.
    Smith AL. Barbiturate protection in cerebral hypoxia. Anesthesiology 1977; 47: 285–93.PubMedCrossRefGoogle Scholar
  9. 9.
    Stanski DR, Mihm FG, Rosenthal MH, et al. Pharmacokinetics of high-dose thiopental used in cerebral resuscitation. Anesthesiology 1980; 53 (2): 169–71.PubMedCrossRefGoogle Scholar
  10. 10.
    Steen PA, Michenfelder JD. Mechanisms of barbiturate protection. Anesthesiology 1980; 53: 183–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Turcant A, Delhumeau A, Premel-Cabic A, et al. Thiopental pharmacokinetics under conditions of long-term infusion. Anesthesiology 1985; 63 (1): 50–4.PubMedCrossRefGoogle Scholar
  12. 12.
    Airey IL, Smith PA, Stoddart JC. Plasma and cerebrospinal fluid barbiturate levels during prolonged continuous thiopentone infusion. Anaesthesia 1982; 37: 328–31.PubMedCrossRefGoogle Scholar
  13. 13.
    Brown AS, Horton JM. Status epilepticus treated by intravenous infusions of thiopentone sodium. BMJ 1967; 1: 27–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Cloyd JC, Wright BD, Perrier D. Pharmacokinetic properties of thiopental in two patients treated for uncontrollable seizures. Epilepsia 1979; 20 (3): 313–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Partinen M, Kovanen J, Nilsson E. Status epilepticus treated by barbiturate anaesthesia with continous monitoring of cerebral function. BMJ 1981; 282: 520–1.PubMedCrossRefGoogle Scholar
  16. 16.
    Mark LC, Burns JJ, Brand L, et al. The passage of thiopental and their oxygen analogs into brain. J Pharmacol Exp Ther 1958; 123: 70–3.PubMedGoogle Scholar
  17. 17.
    Harvey SC. Hypnotics and sedatives. In: Gilman AG, Goodman LS, Gilman A, editors. The pharmacological basis of therapeutics. New York: MacMillan Publishing Co. Inc., 1981: 352–75.Google Scholar
  18. 18.
    Brodie BB, Kurz H, Schanker LS. The importance of dissociation constant and lipid solubility influencing the passage of drugs into the cerebrospinal fluid. J Pharmacol Exp Ther 1960; 130: 20–5.PubMedGoogle Scholar
  19. 19.
    Bush MT, Berry G, Hume A. Ultra-short acting barbiturates as oral hypnotic agents in man. Clin Pharmacol Ther 1966; 7: 373–8.PubMedGoogle Scholar
  20. 20.
    Dayton PG, Perel JM, Landrau MA, et al. The relationship between binding of thiopental to plasma and its distribution into adipose tissue in man, as measured by a spectrophotofluorometric method. Biochem Pharmacol 1967; 16: 2321–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Kane PO, Smith SE. Thiopentone and buthalitone: the relationship between depth of anaesthesia, plasma concentration and protein binding. Br J Pharmacol 1959; 14: 261–4.Google Scholar
  22. 22.
    Brodie BB, Mark LC, Papper EM, et al. The fate of thiopental in man and a method for its estimation in biological material. J Pharmacol Exp Ther 1950; 98: 85–96.PubMedGoogle Scholar
  23. 23.
    Brodie BB, Hogben CAM. Some physico-chemical factors in drug action. J Pharm Pharmacol 1957; 9: 345–80.PubMedCrossRefGoogle Scholar
  24. 24.
    Carroll FI, Smith D, Mark LC, et al. Determination of optically active thiopental thiamytal and their metabolites in human urine. Drug Metab Dispos 1977; 5 (4): 343–54.PubMedGoogle Scholar
  25. 25.
    Christensen JH, Lee IS. Anesthetic potency and acute toxicity of optically active disubstituted barbituric acids. Toxicol Appl Pharmacol 1973; 26: 495–503.PubMedCrossRefGoogle Scholar
  26. 26.
    Haley TJ, Gidley JT. Pharmacology of thiopental stereoisomers. Fed Proc Fed Am Soc Exp Biol 1970; 29: 438.Google Scholar
  27. 27.
    Haley TJ, Gidley JT. Pharmacological comparison of R(+), S(−) and racemic thiopentone in mice. Eur J Pharmacol 1976; 36 (1): 211–4.PubMedCrossRefGoogle Scholar
  28. 28.
    Stanski DR, Burch PG, Harapat SH, et al. Pharmacokinetics and anesthetic potency of a thiopental isomer. J Pharm Sci 1983; 72 (8): 937–40.PubMedCrossRefGoogle Scholar
  29. 29.
    Becker KE. Plasma levels of thiopental necessary for anesthesia. Anesthesiology 1978; 49: 192–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Van Hamme MJ, Ghoneim MM. A sensitive gas Chromatograph assay for thiopentone in plasma. Br JAnaesth 1978; 50(2): 143–5.Google Scholar
  31. 31.
    Braddock LI, Marec N. The gas Chromatographic analysis of sub-microgram quantities of barbiturates using a flame ionization detector. J Gas Chromatogr 1965; 274–7.Google Scholar
  32. 32.
    Schepens P, Heyndrickx A. Placental transfer of thiopental. Eur J Toxicol 1975; 8 (2): 87–93.Google Scholar
  33. 33.
    Becker Jr KE. Gas Chromatographie assay for free and total plasma levels of thiopental. Anesthesiology 1976; 45 (6): 656–60.PubMedCrossRefGoogle Scholar
  34. 34.
    Jung D, Mayersohn M, Perrier D. Gas-chromatographic assay for thiopental in plasma, with use of a nitrogen-specific detector. Clin Chem 1981; 27 (1): 113–5.PubMedGoogle Scholar
  35. 35.
    Burch PG, Stanski DR. Decreased protein binding and thiopental kinetics. Clin Pharmacol Ther 1982; 32 (2): 212–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Christensen JH, Andreasen F. Individual variation in response to thiopental. Acta Anaesthesiol Scand 1978; 22: 303–13.PubMedCrossRefGoogle Scholar
  37. 37.
    Burch PG, Stanski DR. The role of metabolism and protein binding in thiopental anesthesia. Anesthesiology 1983; 58: 146–52.PubMedCrossRefGoogle Scholar
  38. 38.
    Homer TD, Stanski DR. The effect of increasing age on thiopental disposition and anesthetic requirement. Anesthesiology 1985; 62: 714–24.PubMedCrossRefGoogle Scholar
  39. 39.
    Sorbo S, Hudson RJ, Loomis J. The pharmacokinetics of thiopental used in pediatrie surgical patients. Anesthesiology 1984; 61: 666–70.PubMedCrossRefGoogle Scholar
  40. 40.
    Hudson RJ, Stanski DR, Saidman LJ, et al. Amodel for studying depth of anesthesia and acute tolerance to thiopentone. Anesthesiology 1983; 59: 301–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Hudson RJ, Stanski DR, Burch PG. Pharmacokinetics of methohexital and thiopental in surgical patients. Anesthesiology 1983; 59: 215–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Pandele G, Chaux F, Salvadori C, et al. Thiopental pharmacokinetics in patients with cirrhosis. Anesthesiology 1983; 59: 123–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Morgan DJ, Blackman GL, Pauli JD, et al. Pharmacokinetics and plasma binding of thiopental: Pt I. Studies in surgical patients. Anesthesiology 1981; 54 (6): 468–73.PubMedCrossRefGoogle Scholar
  44. 44.
    Morgan DJ, Blackman GL, Pauli JD, et al. Pharmacokinetics and plasma binding of thiopental: Pt II. Studies at Cesarean section. Anesthesiology 1981; 54 (6): 474–80.PubMedCrossRefGoogle Scholar
  45. 45.
    Blackman GL, Jordan GJ, Pauli JD. Analysis of thiopentone in human plasma by high-performance liquid chromatography. J Chromatogr 1978; 145 (3): 492–5.PubMedCrossRefGoogle Scholar
  46. 46.
    Nicot G, Lachatre G, Valette JP, et al. Dosage plasmatique du phénobarbital, pentobarbital et penthiobarbital par Chromatographie liquide à haute performance. Thérapie 1984; 39: 361–7.PubMedGoogle Scholar
  47. 47.
    Taylor JD, Richards RK, Tabern DL. Metabolism of S35 thiopental (Pentothal): chemical and paper Chromatographic studies of S35 excretion by the rat and monkey. J Pharmacol Exp Ther 1953; 104: 93–101.Google Scholar
  48. 48.
    Jung D, Mayersohn M, Perrier D. The ‘ultra-free’ ultrafiltration technique compared with equilibrium dialysis for determination of unbound thiopental concentrations in serum. Clin Chem 1981; 27(1): 166–8.Google Scholar
  49. 49.
    Ghoneim MM, Pandya HB, Kelley SE, et al. Binding of thiopental to plasma proteins: effects on distribution in the brain and heart rats. Anesthesiology 1976; 45 (6): 635–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Chaplin MD, Roszkowski AP, Richards RK. Displacement of thiopental from plasma proteins by non-steroidal antiinflammatory agents. Proc Soc Exp Biol Med 1973; 143: 667–71.PubMedGoogle Scholar
  51. 51.
    Patel VK, Johnson GE. The influence of chronic ethanol consumption on the distribution of thiopental in rats. Can J Physiol Pharmacol 1975; 53 (4): 669–72.PubMedCrossRefGoogle Scholar
  52. 52.
    Christensen JH, Andreasen F. Determination of thiopental by high pressure liquid chromatography. Acta Pharmacol Toxicol 1979; 44 (4): 260–3.CrossRefGoogle Scholar
  53. 53.
    Shiu GK, Nemoto EM. Simple, rapid and sensitive reversedphase high-performance liquid Chromatographic method for thiopental and pentobarbital determination in plasma and brain tissue. J Chromatogr 1982; 227 (1): 207–12.PubMedCrossRefGoogle Scholar
  54. 54.
    Girard I, Coquel C, Gollion B, et al. Dosage plasmatique du thiopental par Chromatographie liquide: application au suivi thérapeutique. J Pharm Clin 1992; 11: 105–8.Google Scholar
  55. 55.
    Faure O, Jarry C, Demarquez JJ, et al. Dosage du thiopental chez le nouveau-né par Chromatographie liquide haute performance. Bull Soc Pharm Bord 1981; 120: 113–9.Google Scholar
  56. 56.
    Huang JL, Mather LE, Duke CC. High-performance liquid Chromatographie determination of thiopentone enantiomers in sheep plasma. J Chromatogr B Biomed Appl 1995; 673: 245–50.PubMedCrossRefGoogle Scholar
  57. 57.
    Stanski DR, Hudson RJ, Homer TD, et al. Pharmacometrics: pharmacodynamic modeling of thiopental anesthesia. J Pharmacokinet Biopharm 1984; 12 (2): 223–40.PubMedGoogle Scholar
  58. 58.
    Price HL, Dundee JW, Conner MD. Rates of uptake and release of thiopental by human brain; relation to kinetics of thiopental anesthesia. Anesthesiology 1957; 18: 171.CrossRefGoogle Scholar
  59. 59.
    Pierce Jr EC, Lambertsen CJ, Deutsch S, et al. Cerebral circulation and metabolism during thiopental anesthesia and hyperventilation in man. J Clin Invest 1962; 41: 1664–71.PubMedCrossRefGoogle Scholar
  60. 60.
    Kassell NF, Hitchon PW, Gerk MK, et al. Alterations in cerebral blood flow, oxygen metabolism and cerebral activity produced by high dose thiopental. Neurosurgery 1980; 7: 598–603.PubMedCrossRefGoogle Scholar
  61. 61.
    Michenfelder JD. The interdependency of cerebral functional and metabolic effects following massive doses of thiopental in the dog. Anesthesiology 1974; 41: 231–6.PubMedCrossRefGoogle Scholar
  62. 62.
    Steen PA, Michenfelder JD. Cerebral protection with barbiturates: relation to anesthetic effect. Stroke 1978; 9: 140–2.PubMedCrossRefGoogle Scholar
  63. 63.
    Astrup J, Symon L, Branston NM, et al. Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. Stroke 1977; 8: 51–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Stuart LA, Rosenberg PA. Mechanisms of disease: excitatory amino acids as a final common pathway for neurological disorders. N Engl J Med 1994; 330 (9): 613–22.CrossRefGoogle Scholar
  65. 65.
    Demopoulous HB, Flamm ES, Pietronigro DD, et al. The free radical pathology and the microcirculation in the major central nervous system disorders. Acta Physiol Scand 1980; 492 Suppl.: 91–119.Google Scholar
  66. 66.
    Majewska MD, Strosznajder J, Lazarewicz J. Effect of ischemie anoxia and barbiturate anesthesia on free radical oxidation of mitochondrial phospholipids. Brain Res 1978; 158: 423–34.PubMedCrossRefGoogle Scholar
  67. 67.
    Eriksson K, Baer M, Kilpinen P, et al. Effects of long barbiturate anaesthesia on eight children with severe epilepsy. Neuropediatrics 1993; 24: 281–5.PubMedCrossRefGoogle Scholar
  68. 68.
    Chamberlain JH, Seed RGFL, Chung DCW. Effect of thiopentone on myocardial function. Br J Anaesth 1977; 49: 865–70.PubMedCrossRefGoogle Scholar
  69. 69.
    Lange H, Stephan H, Zielmann S, et al. Hepatische elimination von thiopental bei koronarchirurgischen patienten. Anaesthesist 1992; 41: 171–8.PubMedGoogle Scholar
  70. 70.
    Baxter AD. Two cases of untoward sequelae associated with thiopentone. Anaesthesia 1978 Apr; 33 (4): 349–52.PubMedCrossRefGoogle Scholar
  71. 71.
    Fox S, Wilkinson RD, Rabow FI. Thiopental anaphylaxis: a case and a method for diagnosis. Anesthesiology 1971; 35 (6): 655–7.PubMedCrossRefGoogle Scholar
  72. 72.
    Coulbois B. Choc anaphylactique grave au cours d’une anesthésie au penthobarbital: intérêt du test de transformation lymphoblastique. Ann Anesthesiol Fr 1973; 14 (3): 259–63.Google Scholar
  73. 73.
    Yasuda T, Yamaba T, Sawazaki K, et al. Postmortem concentrations of thiopental in tissues: a sudden death case. Int J Legal Med 1993; 105: 239–41.PubMedCrossRefGoogle Scholar
  74. 74.
    Moudgil GC. Effect of premedicants, intravenous anaesthetic agents and local anaesthetics on phagocytosis in vitro. Can Anaesth Soc J 1981; 28 (6): 597–602.PubMedCrossRefGoogle Scholar
  75. 75.
    Neuwelt EA, Kikuchi K, Hill SA, et al. Barbiturate inhibition of lymphocyte function: differing effects of various barbiturates used to induce coma. J Neurosurg 1982; 56: 254–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Schmucker P, Hammer C, Peter K, et al. Influence of thiopentone on lymphocyte-transformation in vitro [abstract]. Anesthesiologie 1984; 61A: 355.Google Scholar
  77. 77.
    Edwards R, Ellis FR. Clinical significance of thiopentone binding to haemoglobin and plasma protein. Br J Anaesth 1973; 45: 891–3.PubMedCrossRefGoogle Scholar
  78. 78.
    Aveling W, Bardshaw AD, Crankshaw DP. The effect of speed of injection on the potency of anaesthetic induction agents. Anaesth Intensive Care 1978; 6: 116–9.PubMedGoogle Scholar
  79. 79.
    Avram MJ, Krejcie TC, Henthorn TK. The relationship of age to the pharmacokinetics of early drug distribution: the concurrent disposition of thiopental and indocyanine green. Anesthesiology 1990; 72: 403–11.PubMedCrossRefGoogle Scholar
  80. 80.
    Christensen JH, Andreasen F, Jansen JA. Pharmacokinetics of thiopentone in a group of young women and a group of young men. Br J Anaesth 1980; 52 (9): 913–8.PubMedCrossRefGoogle Scholar
  81. 81.
    Christensen JH, Andreasen F, Jansen JA. Influence of age and sex on the pharmacokinetics of thiopentone. Br J Anaesth 1981; 53 (11): 1189–95.PubMedCrossRefGoogle Scholar
  82. 82.
    Jung D, Mayersohn M, Perrier D, et al. Thiopental disposition as a function of age in female patients undergoing surgery. Anesthesiology 1982; 56,: 263–8.PubMedCrossRefGoogle Scholar
  83. 83.
    Wulfsohn NL, Joshi CW. Thiopentone dosage based on lean body mass. Br J Anaesth 1969; 41: 516–21.PubMedCrossRefGoogle Scholar
  84. 84.
    Hu OYP, Chu KM, Liu HS, et al. Reinduction of the hypnotic effects of thiopental with NSAIDs by decreasing thiopental plasma protein binding in humans. Acta Anaesthesiol Scand 1993; 37: 258–61.PubMedCrossRefGoogle Scholar
  85. 85.
    Swerdlow BN, Holley FO, Maitre PO, et al. Chronic alcohol intake does not change thiopental anesthetic requirement, pharmacokinetics, or pharmadynamics. Anesthesiology 1990; 72: 455–61.PubMedCrossRefGoogle Scholar
  86. 86.
    Gentry WB, Krejcie TC, Henthorn TK, et al. Effect of infusion rate on thiopental dose-response relationships: assessment of a pharmacokinetic-pharmacodynamic model. Anesthesiology 1994; 81: 316–24.PubMedCrossRefGoogle Scholar
  87. 87.
    Bührer M, Mappes A, Lauber R, et al. Dexmedetomidine decreases thiopental dose requirement and alters distribution pharmacokinetics. Anesthesiology 1994; 80: 1216–27.PubMedCrossRefGoogle Scholar
  88. 88.
    Avram MJ, Sanghvi R, Henthorn TK, et al. Determinants of thiopental induction doserequirements. Anesth Analg 1993; 76: 10–7.PubMedCrossRefGoogle Scholar
  89. 89.
    Couderc E, Ferrier C, Haberer JP, et al. Thiopentone pharmacokinetics in patients with chronic alcoholism. Br J Anaesth 1984; 56: 1393–6.PubMedCrossRefGoogle Scholar
  90. 90.
    Jung D, Mayersohn M, Perrier D, et al. Thiopental disposition in lean and obese patients undergoing surgery. Anesthesiology 1982; 56: 269–74.PubMedCrossRefGoogle Scholar
  91. 91.
    Henthorn TK, Michael JA, Krejecie TC. Intravascular mixing and drug distribution: the concurrent disposition of thiopental and indocyanine green. Clin Pharmacol Ther 1989; 45 (1): 56–65.PubMedCrossRefGoogle Scholar
  92. 92.
    Ghoneim MM, Van Hamme MJ. Pharmacokinetics of thiopentone: effects of enflurane and nitrous oxide anaesthesia and surgery. Br J Anaesth 1978; 50: 1237–42.PubMedCrossRefGoogle Scholar
  93. 93.
    Esener Z, Sarihasan B, Guven H, et al. Thiopentone and etomidate concentrations in maternal and umbilical plasma, and in colostrum. Br J Anaesth 1992; 69: 586–8.PubMedCrossRefGoogle Scholar
  94. 94.
    Mark LC, Brand L, Kamvyssi S, et al. Thiopental metabolism by human liver in vivo and in vitro. Nature 1965; 206: 1117–9.PubMedCrossRefGoogle Scholar
  95. 95.
    Loft S, Jensen V, Rorsgaard S. Influence of moderate alcohol intake on wakening plasma thiopental concentration. Acta Anaesthesiol Scand 1983; 27: 266–9.PubMedCrossRefGoogle Scholar
  96. 96.
    Csögor SI, Kerek SF. Enhancement of thiopentone anaesthesia by sulfafurazole. Br J Anaesth 1970; 42: 988–90.PubMedCrossRefGoogle Scholar
  97. 97.
    Christensen JH, Andreasen F, Jansen JA. Thiopentone sensitivity in young and elderly women. Br J Anaesth 1983; 55: 33–40.PubMedCrossRefGoogle Scholar
  98. 98.
    Dundee JW. Thiopentone narcosis in the presence of hepatic dysfunction. Br J Anaesth 1952; 24: 81–100.PubMedCrossRefGoogle Scholar
  99. 99.
    Brodie BB, Mark LC, Lief PA, et al. Acute tolerance to thiopental. J Pharmacol Exp Ther 1951; 102: 215–8.PubMedGoogle Scholar
  100. 100.
    Brand L, Mazzia VDB, Poznak AV, et al. Lack of correlation between electroencephelographic effects and plasma concentrations of thiopentone. Br J Anaesth 1961; 33: 92–6.CrossRefGoogle Scholar
  101. 101.
    Crankshaw DP, Edwards NE, Blackman GL, et al. Evaluation of infusion regimens for thiopentone as a primary anesthetic agent. Eur J Clin Pharmacol 1985; 28: 543–52.PubMedCrossRefGoogle Scholar
  102. 102.
    Dundee JW, Price HL, Dripps RD. Acute tolerance to thiopentone in man. Br J Anaesth 1956; 28: 344–52.PubMedCrossRefGoogle Scholar
  103. 103.
    Dundee JW. The influence of body weight, sex and age on the dosage of thiopentone. Br J Anaesth 1954; 26: 164–73.PubMedCrossRefGoogle Scholar
  104. 104.
    Mark LC, Burns JJ, Campomanes CI, et al. The passage of thiopental into the brain. J Pharmacol Exp Ther 1957; 119: 35–8.PubMedGoogle Scholar
  105. 105.
    Shideman FE, Gould TC, Winters WD, et al. The distribution and in vivo rate of metabolism of thiopental. J Pharmacol Exp Ther 1953; 107: 368–78.PubMedGoogle Scholar
  106. 106.
    Stanski DR, Maitre PO. Population pharmacokinetics and pharmacodynamics of thiopental: the effect of age revisited. Anesthesiology 1990; 72: 412–22.PubMedCrossRefGoogle Scholar
  107. 107.
    Fraioli RL, Sheffer LA, Steffenson JL. The 0.5 MAC equivalent of thiopental: recent progress in anesthesiology and resuscitation. In: Arias A, Laiaurado R, Nalda MA, et al., editors. Amsterdam: Excerpta Medica, 1975; 167–9.Google Scholar
  108. 108.
    Cote CJ, Goridsouzian NG, Liu LMP, et al. The dose response of intravenous thiopental for the induction of general anesthesia in unpremedicated children. Anesthesiology 1981; 55: 703–5.PubMedCrossRefGoogle Scholar
  109. 109.
    Kiersey DK, Bickford RG, Faulconer JA. Electroencephalographic patterns produced by thiopenthal sodium during surgical operations: description and classification. Br J Anaesth 1951; 23: 141–52.PubMedCrossRefGoogle Scholar
  110. 110.
    Levy WJ, Shapiro HM, Maruchak G, et al. Automated EEG processing for intraoperative monitoring: a comparison of techniques. Anesthesiology 1980; 53: 223–36.PubMedCrossRefGoogle Scholar
  111. 111.
    Rampil IJ, Sasse FJ, Smith NT, et al. Spectral edge frequency. Anew correlate of anesthetic depth. Anesthesiology 1980; 53 Suppl.: 12.CrossRefGoogle Scholar
  112. 112.
    Ebling WF, Danhof M, Stanski DR. Pharmacodynamic characterization of the electroencephalographic effects of thiopental in rats. J Pharmacokinet Biopharm 1991; 19: 123–43.PubMedGoogle Scholar
  113. 113.
    Hung OR, Varvel JR, Shafer SL, et al. Quantitation of thiopental anesthetic depth with clinical stimuli. Can J Anaesth 1990; 37 Suppl.: 18.Google Scholar
  114. 114.
    Hung OR, Varvel JR, Shafer SL, et al. Thiopental pharmacodynamics: II. Quantitation of clinical and electroencephalographic depth of anesthesia. Anesthesiology 1992; 77: 237–44.PubMedCrossRefGoogle Scholar
  115. 115.
    Gustafsson LL, Ebling WF, Osaki E, et al. Plasma concentration clamping in the rat using a computer-controlled infusion pump. Pharm Res 1992; 9: 800–7.PubMedCrossRefGoogle Scholar
  116. 116.
    Gustafsson LL, Ebling WF, Osaki E, et al. Quantitation of depth of thiopental anesthesia in the rat. Anesthesiology 1996; 84: 415–27.PubMedCrossRefGoogle Scholar
  117. 117.
    Scott LT. Dosage of anaesthetics. Lancet 1953; II: 835.CrossRefGoogle Scholar
  118. 118.
    Dundee JW, Richards RK. Effect of azotemia upon the action of intravenous barbiturate anesthesia. Anesthesiology 1954; 15 (4): 333–6.PubMedCrossRefGoogle Scholar
  119. 119.
    Dundee JW, Annis D. Barbiturate narcosis in uraemia. Br J Anaesth 1955; 27: 114–23.PubMedCrossRefGoogle Scholar
  120. 120.
    Dundee JW, Gray TC. Variation in response to relaxant drugs. Lancet 1951; II: 1015.CrossRefGoogle Scholar
  121. 121.
    Dundee JW, Hassard TH, McCowan WAW, et al. The induction dose of thiopentone. Anaesthesia 1982; 37: 1176–84.PubMedCrossRefGoogle Scholar
  122. 122.
    Christensen JH, Andreasen F, Jansen JA. Pharmacokinetics and pharmacodynamics of thiopentone: a comparison between young and elderly patients. Anaesthesia 1982; 37: 398–404.PubMedCrossRefGoogle Scholar
  123. 123.
    Price HL, Kovnat PJ, Safer JN, et al. The uptake of thiopental by body tissues and its relation to the duration of narcosis. Clin Pharmacol Ther 1960; 1 (1): 16–22.Google Scholar
  124. 124.
    Shideman FE, Kelly AR, Adams BJ. The role of the liver in the detoxication of thiopental (Pentothal) and two other thio-barbiturates. J Pharmacol Exp Ther 1947; 91: 331–9.PubMedGoogle Scholar
  125. 125.
    Christensen JH, Andreasen F, Jansen JA. Pharmacokinetics and pharmacodynamics of thiopental in patients undergoing renal transplantation. Acta Anaesthesiol Scand 1983; 27: 513–8.PubMedCrossRefGoogle Scholar
  126. 126.
    Keiltry SR. Anesthesia for the alcoholic patient. Anesth Analg 1969; 48: 659–61.Google Scholar
  127. 127.
    Niazi S. Volume of distibution as a function of time. J Pharm Sci 1976; 65: 452–4.PubMedCrossRefGoogle Scholar
  128. 128.
    Crankshaw DP, Rosier A, Ware M. The short term distribution of thiopentone in the dog. Anaesth Intensive Care 1979; 7 (2): 148–51.PubMedGoogle Scholar
  129. 129.
    Vaughan DP, Tucker GT. General theory for rapidly establishing steady-state drug concentration using two successive constant rate infusions. Eur J Clin Pharmacol 1975; 9: 235–8.PubMedCrossRefGoogle Scholar
  130. 130.
    Wagner JG. A safe method for rapidly achieving plasma concentration plateaus. Clin Pharmacol Ther 1974; 16: 691–700.PubMedGoogle Scholar
  131. 131.
    Shand DG, Desjardins RE, Bjornsson TD, et al. The method of separate exponentials: a simple aid to devising intravenous drug loading regiments. Clin Pharmacol Ther 1981; 29: 542–7.PubMedCrossRefGoogle Scholar
  132. 132.
    Holford NHG. Asize standard for pharmacokinetics. Clin Pharmacokinet 1996; 30 (5): 329–32.PubMedCrossRefGoogle Scholar
  133. 133.
    Hooper CL. The use of pentothal sodium rectally as a basal anesthetic agent. Anesthesiology 1942; 3: 458–9.CrossRefGoogle Scholar
  134. 134.
    Rizzi R, Butera G, Da Rin Betta V. Il tiopentale rettale emulsione nella preanestesia dell’infanzia: considerazioni clinicostatistiche. Minerva Anestesiol 1978; 44: 217–23.PubMedGoogle Scholar
  135. 135.
    White TJ, Siegle RL, Burckart GJ, et al. Rectal thiopental for sedation of children for computed tomography. J Comput Assist Tomogr 1979; 3 (2): 286–8.PubMedCrossRefGoogle Scholar
  136. 136.
    Huguenard P, Boué A, Rodas M. L’anesthésie de base au Nesdonal rectal chez l’enfant. Analgésie 1950; 7: 468–80.Google Scholar
  137. 137.
    Buchmann G. Plasma levels of thiopentone in children after rectal and intravenous administration. Acta Anesthesiol Scand 1996; 24 Suppl.: 23–31.Google Scholar
  138. 138.
    Hogben CAM, Schanker LS, Tocco DJ, et al. Absorption of drugs from the stomach: II. The human. J Pharmacol Exp Ther 1957; 120: 540–5.PubMedGoogle Scholar
  139. 139.
    Carlon GC, Kahn RC, Goldiner PL, et al. Long term infusion of sodium thiopental: hemodynamic and respiratory effects. Crit Care Med 1978; 6: 311–6.PubMedCrossRefGoogle Scholar
  140. 140.
    Garg D, Goldberg R, Woo-Ming R, et al. Pharmacokinetics of thiopental in the asphyxiated neonate. Dev Pharmacol Ther 1988; 11: 213–8.PubMedGoogle Scholar
  141. 141.
    Demarquez JL, Galperine R, Billeaud C, et al. High-dose thiopental pharmacokinetics in brain-injured children and neonates: Pt A. Dev Pharmacol Ther 1987; 10: 292–300.PubMedGoogle Scholar
  142. 142.
    Eyre JA, Wilkinson AR. Thiopentone induced coma after severe birth asphyxia. Arch Dis Child 1986; 61: 1084–9.PubMedCrossRefGoogle Scholar
  143. 143.
    Gold F, Autret E, Maurage C, et al. Utilisation du traitement barbiturique par le thipental dans le choc crânien grave de l’enfant. Agressologie 1982; 23D: 61–3.Google Scholar
  144. 144.
    Bonati M, Marraro G, Celardo A, et al. Thiopental efficacy in phenobarbital-resistant neonatal seizures. Dev Pharmacol Ther 1990; 15: 16–20.PubMedGoogle Scholar
  145. 145.
    Toner W, Howard PJ, McGowan WAW, et al. Another look at acute tolerance to thiopentone. Br J Anaesth 1980; 52: 1005–8.PubMedCrossRefGoogle Scholar
  146. 146.
    Maynert EW, Klingman GI. Acute tolerance to intravenous anesthetics in dogs. J Pharmacol Exp Ther 1960; 128: 192–200.Google Scholar
  147. 147.
    Barratt R, Graham GG, Torda TA. Kinetics of thiopentone in relation to the site of sampling. Br J Anaesth 1984; 56: 1385–91.PubMedCrossRefGoogle Scholar
  148. 148.
    Mark LC, Brand L, Perel JM, et al. Barbiturate stereoisomers: direction for the future [abstract 496 (F23/44)]. Excerpta Med Int Congr Ser 1976; 387: 227.Google Scholar
  149. 149.
    Ebling WF, Wada DR, Stanski DR. From piecewise to full physiologic pharmacokinetic modeling: applied to thiopental disposition in the rat. J Pharmacokinet Biopharm 1994; 22: 259–92.PubMedGoogle Scholar
  150. 150.
    McKechnie FB, Converse JG, Albany NY. Placental transmission of thiopenthal. Am J Obstet Gynecol 1955; 70: 639–44.PubMedGoogle Scholar
  151. 151.
    Finster M, Morishima HO, Mark LC, et al. Tissue thiopental concentrations in the fetus and newborn. Anesthesiology 1972; 36: 155–8.PubMedCrossRefGoogle Scholar
  152. 152.
    Flowers CE, Hill C. The placental transmission of barbiturates and thiobarbiturates and their pharmacological action on the mother and the infant. Am J Obstet Gynecol 1959; 78: 730–40.PubMedGoogle Scholar
  153. 153.
    Kosaka Y, Takahashi T, Mark LC. Intravenous thiobarbiturate anesthesia for cesarean section. Anesthesiology 1969; 31 (6): 489–506.PubMedCrossRefGoogle Scholar
  154. 154.
    Morgan DJ, Beamiss CG, Blackman GL, et al. Urinary excretion of placentally transferred thiopentone of the human neonatale. Dev Pharmacol Ther 1982; 5: 3–4.Google Scholar
  155. 155.
    Saidman LJ, Eger El. The effect of the thiopental metabolism on duration of anesthesia. Anesthesiology 1966; 27 (2): 118–26.PubMedCrossRefGoogle Scholar
  156. 156.
    Igari Y, Sugiyama Y, Awazu S, et al. Comparative physiologically based pharmacokinetics of hexobarbital, phenobarbital, and thiopental in the rat. J Pharmacokinet Biopharm 1982 10 (1): 53–75.PubMedGoogle Scholar
  157. 157.
    Price HL. A dynamic concept of the distribution of thiopental in the human body. Anesthesiology 1960; 21 (1): 40–5.PubMedCrossRefGoogle Scholar
  158. 158.
    Bischoff KB, Dedrick RL. Thiopental pharmacokinetics. J Pharm Sci 1968; 57 (8): 1346–51.PubMedCrossRefGoogle Scholar
  159. 159.
    Gillis PP, De Angelis RJ, Wynn RL. Nonlinear pharmacokinetic model of intravenous anesthesia. J Pharm Sci 1976; 65 (7): 1001–6.PubMedCrossRefGoogle Scholar
  160. 160.
    Brodie BB. Physiological disposition and chemical fate of thiobartiturates in the body. Fed Proc 1952; 11: 632–9.PubMedGoogle Scholar
  161. 161.
    Brodie BB, Bernstein E, Mark LC. The role of body fat in limiting the duration of action of thiopental. J Pharmacol Exp Ther 1952; 105: 421–6.PubMedGoogle Scholar
  162. 162.
    Mark LC. Metabolism of barbiturates in man. Clin Pharmacol Ther 1963; 4 (4): 504–30.Google Scholar
  163. 163.
    Novelli GP, Marsili M, Lorenzi P. Influence of liver metabolism on the actions of althesin and thiopentone. Br J Anaesth 1975; 47 (9); 913–6.PubMedCrossRefGoogle Scholar
  164. 164.
    Sharma RP, Stowe CM, Good AL. Studies on the distribution and metabolism of thiopental in cattle, sheep, goats and swine. J Pharmacol Exp Ther 1970; 172: 128–37.PubMedGoogle Scholar
  165. 165.
    Wada DR, Harashima H, Ebling WF, et al. Effects of thiopental on regional blood flows in the rat. Anesthesiology 1996; 84: 596–604.PubMedCrossRefGoogle Scholar
  166. 166.
    Perl W, Rackow H, Salanitre E, et al. Intertissue diffusion effect for inert fat-soluble gases. J Appl Physiol 1965 Jul; 20 (4): 621–7.PubMedGoogle Scholar
  167. 167.
    Altmayer P, Bûch U, Hutschenreuter K, et al. The volatile anesthetics, halothane, enflurane and isoflurane, influence the distribution of thiopental in man differently. Acta Anaesthesiol Scand 1987; 31: 756–61.PubMedCrossRefGoogle Scholar
  168. 168.
    Christensen JH, Andreasen F, Jensen EB. The binding of thiopental to serum proteins determined by ultrafiltration and equilibrium dialysis. Acta Pharmacol Toxicol 1980; 47: 24–32.CrossRefGoogle Scholar
  169. 169.
    Kurtz H, Trunk H, Weitz B. Evaluation of methods to determine protein-binding of drugs/equilibrium dialysis, ultrafiltration, ultracentrifugation, gel filtration. Arzneimittel Forschung 1977; 7: 1373–80.Google Scholar
  170. 170.
    Kurtz H, Mauser A, Stickel HH. Differences in the binding of drugs to plasma proteins from newborn and adult man: Pt I. Eur J Clin Pharmacol 1977; 11: 463–7.CrossRefGoogle Scholar
  171. 171.
    Russo H, Audran M, Bressolle F, et al. Displacement of thiopental from human serum albumin by associated drugs. J Pharm Sci 1993; 82: 493–7.PubMedCrossRefGoogle Scholar
  172. 172.
    Kurtz H, Michels H, Stickel HH. Differences in the binding of drugs to plasma proteins from newborn and adult man: Pt II. Eur J Clin Pharmacol 1977; 11: 469–72.CrossRefGoogle Scholar
  173. 173.
    Ghoneim MM, Pandya HB. Plasma protein binding of thiopental in patients with impaired renal or hepatic function. Anesthesiology 1975; 42: 545–9.PubMedCrossRefGoogle Scholar
  174. 174.
    Christensen JH, Andreasen F, Jensen EB. The binding of thiopental to human serum albumin at variable pH and temperature. Acta Pharmacol Toxicol 1983; 52 (5): 364–70.CrossRefGoogle Scholar
  175. 175.
    Andreasen F. Protein binding of drugs in plasma from patients with acute renal failure. Acta Pharmacol Toxicol 1973; 32: 417–29.CrossRefGoogle Scholar
  176. 176.
    Christensen JH, Andreasen F, Jansen JA. Pharmacokinetics of thiopental in Caesarian section. Acta Anaesthesiol Scand 1981; 25: 174–9.PubMedCrossRefGoogle Scholar
  177. 177.
    Taeger K, Murr R, Schmiedeck P, et al. Thiopentalkinetic bei hochdosierter Anwendun. Anästh Intensivther Notf Med 1986; 21: 237–44.PubMedCrossRefGoogle Scholar
  178. 178.
    Goldbaum LR, Smith PK. The interaction of barbiturates with serum albumin and its possible relation to their disposition and pharmacological actions. J Pharmacol Exp Ther 1954; 3 (111): 197–209.Google Scholar
  179. 179.
    Sakurai T, Tsuchiya S, Martsumaru H. Characteristics of protein binding of thiobarbiturates and 6-n-propyl-2-thiouracil. Chem Pharm Bull 1980; 28 (2): 508–13.PubMedCrossRefGoogle Scholar
  180. 180.
    Morgan DJ, Toh CT, Blackman GL, et al. Plasma binding of thiopentone in late pregnancy. Br J Clin Pharmacol 1983; 15 (1): 121–3.PubMedCrossRefGoogle Scholar
  181. 181.
    Shoeman DW, Azarnoff DL. The alteration of plasma proteins in uremia as reflected in their ability to bind digitoxin and diphenylhydantoin. Pharmacology 1972; 7: 169–77.PubMedCrossRefGoogle Scholar
  182. 182.
    Kurtz H, Fichtl B. Interrelation between plasma protein binding, rate of injection and the anaesthetic effect of thiopental. Biopharm Drug Dispos 1981; 2 (2): 191–6.CrossRefGoogle Scholar
  183. 183.
    Yoshikawa D, Loehning RW. Thiopental binding to serum albumin. Experientia 1965; 21: 376–7.PubMedCrossRefGoogle Scholar
  184. 184.
    Kaukinen S, Eerola M, Ylitalo P. Prolongation of thiopentone anaesthesia by probenecid. Br J Anaesth 1980; 52: 603–6.PubMedCrossRefGoogle Scholar
  185. 185.
    Russo H, Brès J, Duboin MP, et al. Pharmacokinetics of thiopental after single and multiple intravenous doses in critical care patients. Eur J Clin Pharmacol 1995; 49 (1/2): 127–37.PubMedGoogle Scholar
  186. 186.
    Russo H, Bressolle F, Duboin MP. Pharmacokinetics of highdosage thiopental sodium in patients with cerebral injuries: influential factors on kinetic model and on parameter variability. Clin Drug Investig 1997; 13 (5): 255–69.CrossRefGoogle Scholar
  187. 187.
    Russo H, Bressolle F, Brès J, et al. Nonlinear pharmacokinetics of high-dose thiopental following long term treatment. Clin Drug Investig 1996; 11 (1): 32–42.CrossRefGoogle Scholar
  188. 188.
    Russo H, Bressolle F, Duboin MP. Pharmacokinetics of highdose thiopental in pediatric patients with increased intracranial pressure. Ther Drug Monit 1997; 19: 63–70.PubMedCrossRefGoogle Scholar
  189. 189.
    Le Corre P, Malledant Y, Tanguy M, et al. Non linear disposition of thiopenone following long-term infusion. Eur J Drug Metab Pharmacokinet 1993; 18: 255–9.PubMedCrossRefGoogle Scholar
  190. 190.
    Gould TC, Shideman FE. Degradation of thiopental by a cell free homogenale of liver. J Pharmacol Exp Ther 1951; 101: 14–20.Google Scholar
  191. 191.
    Shideman FE. In vitro metabolims of barbiturates. Fed Proc 1952; 2: 640–6.Google Scholar
  192. 192.
    Bollman JL, Brooks LM, Flock EV, et al. Tissue distribution with time after single intravenous administration of pentothal sodium [sodium ethyl (1-methylbulyl-) and pentothal S35 thiobarbiturate]. Anesthesiology 1950; 11: 1–7.PubMedCrossRefGoogle Scholar
  193. 193.
    Dorfman A, Goldbaum LR. Detoxication of barbiturates. J Pharmacol Exp Ther 1947; 90: 330–7.PubMedGoogle Scholar
  194. 194.
    Gould TC, Shideman FE. The in vitro metabolism of thiopental by a fortified, cell-free tissue preparation of the rat. J Pharmacol Exp Ther 1952; 104: 427–39.PubMedGoogle Scholar
  195. 195.
    Winters WD. Urinary metabolites of thiopental in rat, dog and man. Fed Proc 1957; 16: 347–55.Google Scholar
  196. 196.
    Cooper JR, Brodie BB. Enzymatic oxidation of pentobarbital and thiopental. J Pharmacol Exp Ther 1957; 120: 75–83.PubMedGoogle Scholar
  197. 197.
    Spector E, Shideman FE. Metabolism of thiopyrimidine derivatives: thiamylal, thiopental and thiouracil. Biochem Pharmacol 1959; 2: 182–96.PubMedCrossRefGoogle Scholar
  198. 198.
    Richards RK. Experiments on the inactivation of pentothal. Fed Proc 1947; 6: 188–9.PubMedGoogle Scholar
  199. 199.
    Furano ES, Green NM. Metabolic breakdown of thiopental in man determined by gas Chromatographic analysis of serum barbiturate levels. Anesthesiology 1963; 24: 796–800.PubMedCrossRefGoogle Scholar
  200. 200.
    Chan HNJ, Morgan DJ, Crankshaw DP, et al. Pentobarbitone formation during thiopental infusion. Anaesthesia 1985; 40; 1155–9.PubMedCrossRefGoogle Scholar
  201. 201.
    Watson WA, Godley PJ, Garriott JC, et al. Blood pentobarbital concentrations during thiopental therapy. Drug Intell Clin Pharm 1983; 20: 283–7.Google Scholar
  202. 202.
    Wood HB, Horning EC. 5-Ethyl-5-(l-methyl-3-carboxypropyl)-2-barbituric acid and its thio analog: metabolites from pentobarbital and thiopental. J Am Chem Soc 1953; 75: 5511–3.CrossRefGoogle Scholar
  203. 203.
    Carroll FI, Philip A. 5-ethyl-5-(l-methyl-3-carboxypropyl)- barbituric acid. Organic Preparations Procedures 1970; 2 (3): 223–4.CrossRefGoogle Scholar
  204. 204.
    Carroll FI, Philip A. Synthesis of (R)-5-alkyl-5-(1′-methyl-3′-carboxypropyl) barbituric acids and (R)-5-alkyl-5-(1′-methyl-3′-carboxypropyl)-2-thiobarbituric acids. Organic Preparations Procedures Int 1978; 10 (1): 21–7.CrossRefGoogle Scholar
  205. 205.
    Dickert YJ, Shea PJ, McCarty LR. The synthesis and pharmacological activity of 5-ethyl-5-(3-hydroxy-l-methylbutyl) barbituric acid. J Med Chem 1966; 9: 249.PubMedCrossRefGoogle Scholar
  206. 206.
    Carroll FI, Blackwell JT. Synthesis of (1′ RS, 3′SR)- and (1′ RS, 3′RS)-5-ethyl-5-(3′-hydroxy-1305-methylbutyl) barbituric acid. Chem Commun 1970: 1616–7.Google Scholar
  207. 207.
    Maynert EW, Dawson JM. Ethyl (3-hydroxy-l-methylbutyl) barbituric acids as metabolites of pentobarbital. J Biol Chem 1952; 195: 389–95.PubMedGoogle Scholar
  208. 208.
    Rowland M, Tozer TN. Clinical pharmacokinetics: concepts and applications. Philadelphia: Lea and Febiger, 1980: 66–70.Google Scholar
  209. 209.
    Wilkinson GR, Shand DG. Aphysiological approach to hepatic drug clearance. Clin Pharmacol Ther 1975; 18: 377–90.PubMedGoogle Scholar
  210. 210.
    Russo H, Brès J, Duboin MP, et al. Variability of thiopental clearance in routine critical care patients. Eur J Clin Pharmacol 1995; 48 (6): 479–87.PubMedCrossRefGoogle Scholar
  211. 211.
    Russo H, Simon N, Duboin MP, et al. Population pharmacokinetics of high-dose thiopental in patientwith cerebral injuries. Clin Pharmacol Ther 1997; 62 (1): 15–20.PubMedCrossRefGoogle Scholar
  212. 212.
    Bayliff CD, Schwartz ML, Hardy BG. Pharmacokinetics of high-dose pentobarbital in severe head trauma. Clin Pharmacol Ther 1985; 38 (4): 457–61.PubMedCrossRefGoogle Scholar
  213. 213.
    Heinemeyer G, Roots I, Dennhardt R. Monitoring of pentobarbital plasma levels in critical care patients suffering from increased intracranial pressure. Ther Drug Monit 1986; 8: 145–50.PubMedCrossRefGoogle Scholar
  214. 214.
    Wermeling DP, Blouin RA, Porter WH, et al. Pentobarbital pharmacokinetics in patients with severe head injury. Drug Intell Clin Phar 1987; 21: 459–63.Google Scholar
  215. 215.
    Bruce DA, Gennarelli TA, Langfitt TW. Resuscitation from coma due to head injury. Crit Care Med 1978; 6: 254–69.PubMedCrossRefGoogle Scholar
  216. 216.
    Totis M, Batt AM, Siest G. Les cytochromes P450 hépatiques chez l’homme. J Pharm Clin 1991; 10: 93–8.Google Scholar
  217. 217.
    Knodell RG, Duvey RK, Wilkinson GR, et al. Oxidative metabolism of hexobarbital in human liver: relationship to polymorphic S-mephenytoin 4-hydroxylation. J Pharmacol Exp Ther 1988; 245: 845–9.PubMedGoogle Scholar
  218. 218.
    Watkins PB, Wrighton SA, Maurel P, et al. Identification of an inducible form of cytochrome P450 in human liver. Proc Natl Acad Sci USA 1985; 82: 6310–7.PubMedCrossRefGoogle Scholar
  219. 219.
    Baldeo WC, Gilbert JN, Powell JW. Multidose studies in the human metabolism of pentobarbitone. Eur J Drug Metab Pharmacokinet 1980; 5: 75–80.PubMedCrossRefGoogle Scholar
  220. 220.
    Russo H, Duboin MP, Bressolle F, et al. Time-dependent pharmacokinetics of high dose thiopental infusion in intensive care patients. Pharmaceut Res 1997; 14(11): 1583–9.CrossRefGoogle Scholar
  221. 221.
    Hughes MA, Glass PSA, Jacobs JR. Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology 1992; 76: 334–41.PubMedCrossRefGoogle Scholar
  222. 222.
    Davis M, Simmons CJ, Dordoni B, et al. Induction of hepatic enzymes during normal human pregnancy. Br J Obstet Gynaecol 1973; 80: 690–4.CrossRefGoogle Scholar
  223. 223.
    Rubin E, Lieber CS. Hepatic microsomal enzymes in man and rat: induction and inhibition by ethanol. Science 1968 Nov 8; 162 (854): 690–1.PubMedCrossRefGoogle Scholar
  224. 224.
    Rahn E, Dayton PG, Frederickson EL. Lack of effect of halothane on the metabolism of thiopentone in man. Br J Anaesth 1969; 41: 503–5.PubMedCrossRefGoogle Scholar
  225. 225.
    Cooperman LH. Effects of anaesthetics on the splanchnic circulation. Br J Anaesth 1972 Sep; 44 (9): 967–70.PubMedCrossRefGoogle Scholar
  226. 226.
    Juhl B, Einer-Jensen N. Hepatic blood flow and cardiac output during Fluoromar anaesthesia: an animal study. Acta Anaesthesiol Scand 1976; 20 (4): 271–7.PubMedCrossRefGoogle Scholar
  227. 227.
    Swartz RD, Sidell FR, Cucinell SA. Effects of physical stress on the disposition of drugs eliminated by the liver in man. J Pharmacol Exp Ther 1974; 188 (1): 1–7.PubMedGoogle Scholar
  228. 228.
    Brown BR. The diphasic action of halothane on the oxidative metabolism of drugs by the liver: an in vitro study in the rat. Anesthesiology 1971 Sep; 35 (3): 241–6.PubMedCrossRefGoogle Scholar
  229. 229.
    Chung H, Brown DR. Mechanism of the effect of acute ethanol on hexobarbital metabolism. Biochem Pharmacol 1976; 25: 1613–6.PubMedCrossRefGoogle Scholar
  230. 230.
    Chung H, Brown DR. The mechanism of the effect of acute stress on hexobarbital metabolism. Toxicol Appl Pharmacol 1976; 37: 313–8.PubMedCrossRefGoogle Scholar
  231. 231.
    Verotta D, Sheiner LB. Pharmacometrics: mean time parameters for generalized physiological flow models (semihomogeneous linear system). J Pharmacokinet Biopharm 1991; 19: 319–31.PubMedGoogle Scholar
  232. 232.
    Henthorn TK, Avram MJ, Krejcie TC, et al. Minimal compartment model of circulatory mixing of indocyanine green. Am J Physiol 1992; 262: H903–10.PubMedGoogle Scholar
  233. 233.
    Mayer S, Maickel RP, Brodie BB. Kinetics of drugs and other foreign compounds into cerebrospinal fluid and brain. J Pharmacol Exp 1959; 127: 205–11.Google Scholar
  234. 234.
    Saidman LJ, Eger El. Uptake and distribution of thiopental after oral, rectal, and intramuscular administration: effects of hepatic metabolism and injection site blood flow. Clin Pharmacol Ther 1973; 14 (1): 12–20.PubMedGoogle Scholar
  235. 235.
    Shanks CA, Avram MJ, Krejcie TC, et al. A pharmacokineticpharmacodynamic model for quantal responses with thiopental. J Pharmacokinet Biopharm 1993; 21: 309–21.PubMedGoogle Scholar

Copyright information

© Adis International Limited 1998

Authors and Affiliations

  • Hélène Russo
    • 1
  • Françoise Bressolle
    • 2
  1. 1.Pharmacie Saint-EloiCentre Hospitalier UniversitaireMontpellierFrance
  2. 2.Faculté de PharmacieLaboratoire de PharmacocinétiqueMontpellierFrance

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