Comparative pharmacokinetics of brotizolam and triazolam in healthy subjects

Pharmacokinetics of oral brotizolam (0.50 mg) and triazolam (0.50 mg) were studied in healthy young volunteers. The plasma concentration profile of brotizolam can be described as a one compartmental open model with first-order absorption. The absorption of triazolam was less regular and in half of the subjects was not consistent with first-order kinetics. Inter-individual variability in absorption rate (peak times) was larger for brotizolam. Mean peak times were 1.1 +/- 1.0 h for brotizolam and 1.2 +/- 0.5 h for triazolam. Mean peak concentrations were 7.3 +/- 3.1 ng/ml and 5.0 +/- 3.9 ng/ml respectively. The elimination half-life of brotizolam was twice that of triazolam with mean values of 5.0 +/- 1.1 h and 2.6 +/- 0.7 h respectively. There was no correlation between the half-lives of the two drugs. Protein unbound fraction was similar for triazolam and brotizolam with mean values of 9.9 +/- 1.5% and 8.4 +/- 0.7% respectively.