Skip to main content
PMC home page
Gut logoLink to Gut
. 1986 Feb;27(2):190–195. doi: 10.1136/gut.27.2.190

Pharmacokinetics and pharmacodynamics of intravenous midazolam in patients with severe alcoholic cirrhosis.

A J MacGilchrist, G G Birnie, A Cook, G Scobie, T Murray, G Watkinson, M J Brodie
PMCID: PMC1433214  PMID: 2936661

Abstract

Midazolam kinetics and psychomotor function were studied after an intravenous dose of 0.075 mg/kg body weight in seven patients with alcoholic cirrhosis and eight control patients. Four of the seven cirrhotics died of complications of their liver disease within six months of the study. The metabolism of midazolam was significantly impaired in the cirrhotic patients (p less than 0.025). These patients also had evidence of greater sedation than the control group for up to six hours after the dose was administered (p less than 0.05). The clearance of midazolam did not correlate significantly with the serum albumin, or bilirubin, or with the kinetics of antipyrine, or indocyanine green. This study shows significant delay in the elimination of midazolam and decreased psychomotor function in patients with severe alcoholic liver disease. Caution is needed in using this drug for premedication in such patients before endoscopy.

Full text

PDF
191

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  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. Branch R. A., Morgan M. H., James J., Read A. E. Intravenous administration of diazepam in patients with chronic liver disease. Gut. 1976 Dec;17(12):975–983. doi: 10.1136/gut.17.12.975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. CAESAR J., SHALDON S., CHIANDUSSI L., GUEVARA L., SHERLOCK S. The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci. 1961 Aug;21:43–57. [PubMed] [Google Scholar]
  6. Cole S. G., Brozinsky S., Isenberg J. I. Midazolam, a new more potent benzodiazepine, compared with diazepam: a randomized, double-blind study of preendoscopic sedatives. Gastrointest Endosc. 1983 Aug;29(3):219–222. doi: 10.1016/s0016-5107(83)72588-5. [DOI] [PubMed] [Google Scholar]
  7. Greenblatt D. J., Locniskar A., Ochs H. R., Lauven P. M. Automated gas chromatography for studies of midazolam pharmacokinetics. Anesthesiology. 1981 Aug;55(2):176–179. doi: 10.1097/00000542-198108000-00014. [DOI] [PubMed] [Google Scholar]
  8. Heizmann P., Ziegler W. H. Excretion and metabolism of 14C-midazolam in humans following oral dosing. Arzneimittelforschung. 1981;31(12A):2220–2223. [PubMed] [Google Scholar]
  9. Hindmarch I. Psychomotor function and psychoactive drugs. Br J Clin Pharmacol. 1980 Sep;10(3):189–209. doi: 10.1111/j.1365-2125.1980.tb01745.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hoyampa A. M., Jr, Branch R. A., Schenker S. The disposition and effects of sedatives and analgesics in liver disease. Annu Rev Med. 1978;29:205–218. doi: 10.1146/annurev.me.29.020178.001225. [DOI] [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. Kraus J. W., Desmond P. V., Marshall J. P., Johnson R. F., Schenker S., Wilkinson G. R. Effects of aging and liver disease on disposition of lorazepam. Clin Pharmacol Ther. 1978 Oct;24(4):411–419. doi: 10.1002/cpt1978244411. [DOI] [PubMed] [Google Scholar]
  13. MacDougall B. R., Westaby D., Theodossi A., Dawson J. L., Williams R. Increased long-term survival in variceal haemorrhage using injection sclerotherapy. Results of a controlled trial. Lancet. 1982 Jan 16;1(8264):124–127. doi: 10.1016/s0140-6736(82)90378-6. [DOI] [PubMed] [Google Scholar]
  14. Macphee G. J., Thompson G. G., Scobie G., Agnew E., Park B. K., Murray T., McColl K. E., Brodie M. J. Effects of cimetidine on carbamazepine auto- and hetero-induction in man. Br J Clin Pharmacol. 1984 Sep;18(3):411–419. doi: 10.1111/j.1365-2125.1984.tb02483.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McConnell J. B., Curry S. H., Davis M., Williams R. Clinical effects and metabolism of diazepam in patients with chronic liver disease. Clin Sci (Lond) 1982 Jul;63(1):75–80. doi: 10.1042/cs0630075. [DOI] [PubMed] [Google Scholar]
  16. Parker G., Roberts C. J. Plasma concentrations and central nervous system effects of the new hypnotic agent zopiclone in patients with chronic liver disease. Br J Clin Pharmacol. 1983 Sep;16(3):259–265. doi: 10.1111/j.1365-2125.1983.tb02159.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Read A. E., Laidlaw J., McCarthy C. F. Effects of chlorpromazine in patients with hepatic disease. Br Med J. 1969 Aug 30;3(5669):497–499. doi: 10.1136/bmj.3.5669.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rowland M., Benet L. Z., Graham G. G. Clearance concepts in pharmacokinetics. J Pharmacokinet Biopharm. 1973 Apr;1(2):123–136. doi: 10.1007/BF01059626. [DOI] [PubMed] [Google Scholar]
  19. Shull H. J., Wilkinson G. R., Johnson R., Schenker S. Normal disposition of oxazepam in acute viral hepatitis and cirrhosis. Ann Intern Med. 1976 Apr;84(4):420–425. doi: 10.7326/0003-4819-84-4-420. [DOI] [PubMed] [Google Scholar]
  20. Smith M. T., Eadie M. J., Brophy T. O. The pharmacokinetics of midazolam in man. Eur J Clin Pharmacol. 1981 Mar;19(4):271–278. doi: 10.1007/BF00562804. [DOI] [PubMed] [Google Scholar]
  21. Whitwam J. G., Al-Khudhairi D., McCloy R. F. Comparison of midazolam and diazepam in doses of comparable potency during gastroscopy. Br J Anaesth. 1983 Aug;55(8):773–777. doi: 10.1093/bja/55.8.773. [DOI] [PubMed] [Google Scholar]
  22. Wilkinson G. R., Shand D. G. Commentary: a physiological approach to hepatic drug clearance. Clin Pharmacol Ther. 1975 Oct;18(4):377–390. doi: 10.1002/cpt1975184377. [DOI] [PubMed] [Google Scholar]
  23. Williams R. L. Drug administration in hepatic disease. N Engl J Med. 1983 Dec 29;309(26):1616–1622. doi: 10.1056/NEJM198312293092605. [DOI] [PubMed] [Google Scholar]
  24. Williams R. L., Mamelok R. D. Hepatic disease and drug pharmacokinetics. Clin Pharmacokinet. 1980 Nov-Dec;5(6):528–547. doi: 10.2165/00003088-198005060-00002. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES