Summary
The pharmacokinetics of midazolam has been studied in patients recovering from cardiac surgery, who required sedation for postoperative mechanical ventilation. Twelve males (mean age 64.5 years) with severe heart disease received an infusion of midazolam 15 mg·h−1 for 4 h, starting 1 to 3 h post surgery. Multiple blood samples were collected from each patient during the infusion and up to 48–93 h after it. The pharmacokinetic parameters of midazolam were determined using both moment analysis and the program NONMEM.
The average terminal half-life was 10.6 h. The prolonged elimination was mainly due to a decrease in its metabolic clearance (0.25 l·min−1).
The maintenance infusion dose of midazolam in such patients should be reduced. The time to recovery after stopping an infusion depends upon the amount of drug in the body at that time and a simulation of the plasma concentrations after various infusion regimens suggests that recovery will be delayed after prolonged (>48 h) administration of midazolam to these patients. However, after shorter infusions (<12 h), redistribution of the drug away from the site of action was still occurring and recovery would be expected to be relatively rapid.
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Harper KW, Collier PS, Dundee JW, Elliott P, Halliday NJ, Lowry KG (1985) Age and nature of operation influence the pharmacokinetics of midazolam. Br J Anaesth 57: 866–871
Greenblatt DJ, Locniskar A, Ochs HR, Lauven PM (1981) Automated gas chromatography for studies of midazolam pharmacokinetics. Anesthesiology 55: 176–179
Greenblatt DJ, Abernethy DR, Locniskar A, Harmatz JS, Limjuco RA, Shader RI (1984) Effect of age, gender, and obesity on midazolam kinetics. Anesthesiology 61: 27–35
Smith MT, Eadie MJ, O'Rourke T (1981) The pharmacokinetics of midazolam in man. Eur J Clin Pharmacol 19: 271–278
Allonen H, Ziegler G, Klotz U (1981) Midazolam kinetics. Clin Pharmacol Ther 30: 653–661
Shapiro JM, Westphal LM, White PF, Sladen RN, Rosenthal MH (1986) Midazolam infusion for sedation in the intensive care unit: Effect on adrenal function. Anesthesiology 64: 394–398
Byatt CM, Lewis LD, Dawling S; Cochrane GM (1984) Accumulation of midazolam after repeated dosage in patients receiving mechanical ventilation in an intensive care unit. Br Med J 289: 799–800
Byrne AJ, Yeoman PM, Mace P (1984) Accumulation of midazolam in patients receiving mechanical ventilation [letter]. Br Med J 289: 1309
Oldenhof H, de Jong M, Steenhoek A, Janknegt R (1988) Clinical pharmacokinetics of midazolam in intensive care patients, a wide interpatient variability? Clin Pharmacol Ther 43: 263–269
Ha HR, Funk B, Maitre PO, Zbinden AM, Follath F, Thomson DA (1988) Measurement of midazolam in plasma from hospitalized patients as measured by gas liquid chromatography with electron capture detection. Clin Chem 34: 676–679
Sheiner LB, Rosenberg B, Melmon K (1972) Modelling of individual pharmacokinetics for computer aided dosage. Comput Biomed Res 5: 441–459
Kanto JH (1985) Midazolam the first water-soluble benzodiazepine. Pharmacotherapy 5: 138–155
Vozeh S, Katz G, Steiner V, Follath F (1982) Population pharmacokinetic parameters in patients treated with oral mexiletine. Eur J Clin Pharmacol 23: 445–451
Maitre PO, Vozeh S, Heykants J, Thomson DA, Stanski DR (1987) Population pharmacokinetics of alfentanil: The average dose-plasma concentration relationship and interindividual variability in patients. Anesthesiology 66: 3–12
Jusko WJ (1986) Guidelines for collection and analysis of pharmacokinetic data. In: Evans WE, Schentag JJ, Jusko WJ (eds) Applied pharmacokinetics. Applied Therapeutics Inc, San Francisco, pp 9–54
Westphal LM, Cheng EY, White PF, Sladen RN, Rosenthal MH, Sung ML (1987) Use of midazolam infusion for sedation following cardiac surgery. Anesthesiology 67: 257–262
Crevoisier C, Ziegler WH, Eckert M, Heizmann P (1983) Relationship between plasma concentration and effect of midazolam after oral and intravenous administration. Br J Clin Pharmacol 16: 51S-61S
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Maitre, P.O., Funk, B., Crevoisier, C. et al. Pharmacokinetics of midazolam in patients recovering from cardiac surgery. Eur J Clin Pharmacol 37, 161–166 (1989). https://doi.org/10.1007/BF00558225
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DOI: https://doi.org/10.1007/BF00558225