Abstract
The disposition of midazolam was investigated in six patients with congestive heart failure (CHF) and six age- and weight-matched healthy subjects by administering two single doses of the drug (3.75 mg i.v. and 7.5 mg p.o.) separated by 1 week. Serial blood samples were collected for 24 h after each dose and plasma was assayed for midazolam by GC-MS. In the CHF patients, the elimination half-life was prolonged (4 to 4.5 vs less than 3 h), the systemic clearance was lowered (376 vs 551 ml min-1) and the peak plasma drug concentration after the p.o. dose was higher (76 vs 42 ng ml-1). The systemic availability (45 vs 41%), the steady state volume of distribution (111 vs 108 l) and the time of peak plasma drug concentration after the p.o. dose (0.9 vs 0.9 h) were unchanged. The predominant effect of CHF was on the clearance of midazolam which was decreased by 30%. The drug was well tolerated and did not cause any adverse effects.
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Selected References
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- 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]
- Avram M. J., Fragen R. J., Caldwell N. J. Midazolam kinetics in women of two age groups. Clin Pharmacol Ther. 1983 Oct;34(4):505–508. doi: 10.1038/clpt.1983.205. [DOI] [PubMed] [Google Scholar]
- Bornemann L. D., Crews T., Chen S. S., Twardak S., Patel I. H. Influence of food on midazolam absorption. J Clin Pharmacol. 1986 Jan;26(1):55–59. doi: 10.1002/j.1552-4604.1986.tb02903.x. [DOI] [PubMed] [Google Scholar]
- Bornemann L. D., Min B. H., Crews T., Rees M. M., Blumenthal H. P., Colburn W. A., Patel I. H. Dose dependent pharmacokinetics of midazolam. Eur J Clin Pharmacol. 1985;29(1):91–95. doi: 10.1007/BF00547375. [DOI] [PubMed] [Google Scholar]
- 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]
- Greenblatt D. J., Abernethy D. R., Locniskar A., Harmatz J. S., Limjuco R. A., Shader R. I. Effect of age, gender, and obesity on midazolam kinetics. Anesthesiology. 1984 Jul;61(1):27–35. [PubMed] [Google Scholar]
- 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]
- 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]
- Holazo A. A., Winkler M. B., Patel I. H. Effects of age, gender and oral contraceptives on intramuscular midazolam pharmacokinetics. J Clin Pharmacol. 1988 Nov;28(11):1040–1045. doi: 10.1002/j.1552-4604.1988.tb03127.x. [DOI] [PubMed] [Google Scholar]
- Kassai A., Toth G., Eichelbaum M., Klotz U. No evidence of a genetic polymorphism in the oxidative metabolism of midazolam. Clin Pharmacokinet. 1988 Nov;15(5):319–325. doi: 10.2165/00003088-198815050-00004. [DOI] [PubMed] [Google Scholar]
- Klotz U., Mikus G., Zekorn C., Eichelbaum M. Pharmacokinetics of midazolam in relation to polymorphic sparteine oxidation. Br J Clin Pharmacol. 1986 Nov;22(5):618–620. doi: 10.1111/j.1365-2125.1986.tb02946.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klotz U., Ziegler G. Physiologic and temporal variation in hepatic elimination of midazolam. Clin Pharmacol Ther. 1982 Jul;32(1):107–112. doi: 10.1038/clpt.1982.133. [DOI] [PubMed] [Google Scholar]
- Rubio F., Miwa B. J., Garland W. A. Determination of midazolam and two metabolites of midazolam in human plasma by gas chromatography--negative chemical-ionization mass spectrometry. J Chromatogr. 1982 Dec 10;233:157–165. doi: 10.1016/s0378-4347(00)81742-9. [DOI] [PubMed] [Google Scholar]
- Shammas F. V., Dickstein K. Clinical pharmacokinetics in heart failure. An updated review. Clin Pharmacokinet. 1988 Aug;15(2):94–113. doi: 10.2165/00003088-198815020-00002. [DOI] [PubMed] [Google Scholar]
- 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]
- Smith M. T., Heazlewood V., Eadie M. J., Brophy T. O., Tyrer J. H. Pharmacokinetics of midazolam in the aged. Eur J Clin Pharmacol. 1984;26(3):381–388. doi: 10.1007/BF00548771. [DOI] [PubMed] [Google Scholar]