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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1989 May;27(5):629–633. doi: 10.1111/j.1365-2125.1989.tb03428.x

The pharmacokinetics of midazolam following orthotopic liver transplantation.

M P Shelly 1, J S Dixon 1, G R Park 1
PMCID: PMC1379931  PMID: 2667599

Abstract

Seven patients with chronic liver disease received a 10 mg intravenous bolus dose of midazolam immediately following orthotopic liver transplantation. Plasma samples were analysed for midazolam and alpha-hydroxymidazolam by gas chromatography with electron capture detection. Data from three patients could not be evaluated. In the remaining four patients the pharmacokinetics of midazolam were essentially normal but the plasma concentrations of alpha-hydroxy-midazolam were higher than those found in healthy subjects. All patients required further sedation between 0.5 and 5 h later indicating that the duration of action of midazolam was not prolonged. These results suggest that following liver transplantation, patients have considerable drug metabolising capacity either in the liver or at extrahepatic sites.

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Selected References

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  1. Accumulation of midazolam in patients receiving mechanical ventilation. Br Med J (Clin Res Ed) 1984 Nov 10;289(6454):1309–1309. doi: 10.1136/bmj.289.6454.1309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allonen H., Ziegler G., Klotz U. Midazolam kinetics. Clin Pharmacol Ther. 1981 Nov;30(5):653–661. doi: 10.1038/clpt.1981.217. [DOI] [PubMed] [Google Scholar]
  3. Byatt C. M., Lewis L. D., Dawling S., Cochrane G. M. Accumulation of midazolam after repeated dosage in patients receiving mechanical ventilation in an intensive care unit. Br Med J (Clin Res Ed) 1984 Sep 29;289(6448):799–800. doi: 10.1136/bmj.289.6448.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dundee J. W., Collier P. S., Carlisle R. J., Harper K. W. Prolonged midazolam elimination half-life. Br J Clin Pharmacol. 1986 Apr;21(4):425–429. doi: 10.1111/j.1365-2125.1986.tb05217.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dundee J., Halliday N. J., Fee J. P. Midazolam in intensive care. Br Med J (Clin Res Ed) 1984 Dec 1;289(6457):1540–1540. doi: 10.1136/bmj.289.6457.1540-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gerkens J. F., Desmond P. V., Schenker S., Branch R. A. Hepatic and extrahepatic glucuronidation of lorazepam in the dog. Hepatology. 1981 Jul-Aug;1(4):329–335. doi: 10.1002/hep.1840010409. [DOI] [PubMed] [Google Scholar]
  7. Ghabrial H., Desmond P. V., Watson K. J., Gijsbers A. J., Harman P. J., Breen K. J., Mashford M. L. The effects of age and chronic liver disease on the elimination of temazepam. Eur J Clin Pharmacol. 1986;30(1):93–97. doi: 10.1007/BF00614203. [DOI] [PubMed] [Google Scholar]
  8. Greenblatt D. J., Locniskar A., Scavone J. M., Blyden G. T., Ochs H. R., Harmatz J. S., Shader R. I. Absence of interaction of cimetidine and ranitidine with intravenous and oral midazolam. Anesth Analg. 1986 Feb;65(2):176–180. [PubMed] [Google Scholar]
  9. Hamdy N. A., Kennedy H. J., Nicholl J., Triger D. R. Sedation for gastroscopy: a comparative study of midazolam and Diazemuls in patients with and without cirrhosis. Br J Clin Pharmacol. 1986 Dec;22(6):643–647. doi: 10.1111/j.1365-2125.1986.tb02952.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Heizmann P., Eckert M., Ziegler W. H. Pharmacokinetics and bioavailability of midazolam in man. Br J Clin Pharmacol. 1983;16 (Suppl 1):43S–49S. doi: 10.1111/j.1365-2125.1983.tb02270.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Klotz U., Avant G. R., Hoyumpa A., Schenker S., Wilkinson G. R. The effects of age and liver disease on the disposition and elimination of diazepam in adult man. J Clin Invest. 1975 Feb;55(2):347–359. doi: 10.1172/JCI107938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Klotz U., Reimann I. Delayed clearance of diazepam due to cimetidine. N Engl J Med. 1980 May 1;302(18):1012–1014. doi: 10.1056/NEJM198005013021807. [DOI] [PubMed] [Google Scholar]
  13. Klotz U., Reimann I. Influence of cimetidine on the pharmacokinetics of desmethyldiazepam and oxazepam. Eur J Clin Pharmacol. 1980 Nov;18(6):517–520. doi: 10.1007/BF00874666. [DOI] [PubMed] [Google Scholar]
  14. Lloyd-Thomas A. R., Booker P. D. Infusion of midazolam in paediatric patients after cardiac surgery. Br J Anaesth. 1986 Oct;58(10):1109–1115. doi: 10.1093/bja/58.10.1109. [DOI] [PubMed] [Google Scholar]
  15. MacGilchrist A. J., Birnie G. G., Cook A., Scobie G., Murray T., Watkinson G., Brodie M. J. Pharmacokinetics and pharmacodynamics of intravenous midazolam in patients with severe alcoholic cirrhosis. Gut. 1986 Feb;27(2):190–195. doi: 10.1136/gut.27.2.190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ochs H. R., Greenblatt D. J., Verburg-Ochs B., Matlis R. Temazepam clearance unaltered in cirrhosis. Am J Gastroenterol. 1986 Jan;81(1):80–84. [PubMed] [Google Scholar]
  17. Rinetti M., Ascalone V., Colombi Zinelli L., Cisternino M. A pharmacokinetic study on midazolam in compensated liver cirrhosis. Int J Clin Pharmacol Res. 1985;5(6):405–411. [PubMed] [Google Scholar]
  18. Shelly M. P., Mendel L., Park G. R. Failure of critically ill patients to metabolise midazolam. Anaesthesia. 1987 Jun;42(6):619–626. doi: 10.1111/j.1365-2044.1987.tb03086.x. [DOI] [PubMed] [Google Scholar]

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