Pharmacokinetics of brotizolam in healthy subjects following intravenous and oral administration.

Abstract

Pharmacokinetics and bioavailability of brotizolam after i.v. and oral administration were studied in healthy young volunteers. Kinetic parameters after i.v. administration were: volume of distribution 0.66 +/‐ 0.19 1/kg, total plasma clearance 113 +/‐ 28 ml/min, distribution half‐life 11 +/‐ 6 min, and elimination half‐life 4.8 +/‐ 1.4 h (mean values +/‐ s.d.). Kinetic parameters after oral administration were: absorption lag‐time 8 +/‐ 12 min, absorption half‐life 10 +/‐ 11 min, and elimination half‐life 5.1 +/‐ 1.2 h (mean values +/‐ s.d.). Bioavailability of brotizolam was 70 +/‐ 22% when calculated by comparing oral and intravenous area‐under‐curve values, corrected for intra‐individual half‐life differences. An alternative calculation method, which is relatively independent of large clearance variations, provided a bioavailability of 70 +/‐ 24% (range: 47‐117%). 1983 The British Pharmacological Society