Pharmacokinetics of midazolam in the aged.

The pharmacokinetics of midazolam, an imidazo-benzodiazepine derivative, have been studied in 13 subjects over the age of 60 years who received the drug intravenously (0.07 mg kg-1) as an induction agent for endoscopy. Two to three days later, 6 of these subjects received 5 mg of midazolam intramuscularly, and another 6 of the subjects received 10 mg of the drug orally. The plasma concentration-time curves were again studied pharmacokinetically. After intravenous dosing, the mean (+/- SD) elimination half-life (2.14 +/- 1.24 h) showed a statistically significant trend to increase with age in the subjects older than 60 years. While the mean (+/- SD) clearance value (0.30 +/- 0.19 l kg-1h-1) tended to fall with age in the elderly subjects, this trend was not statistically significant. Apparent volume of distribution did not appear to be related to advancing age beyond 60 years, and this parameter (mean +/- SD) did not differ to a statistically significant extent between the aged subjects (0.77 +/- 0.47 l kg-1) and the young subjects studied previously (1.09 +/- 0.58 l kg-1). Atropine premedication did not appear to alter the dispositional parameters of the intravenously administered drug. Intramuscularly administered midazolam was absorbed rapidly. Bioavailability appeared incomplete (F = 0.59 +/- 0.15, mean +/- SD), possibly due to saturable elimination of the drug at the higher plasma levels which were obtained after intravenous midazolam. Oral bioavailability, relative to intravenous, was 0.34 +/- 0.17, (mean +/- SD), with an appreciable but variable lag time (0.74 +/- 0.40 h, mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS)