Bioavailability and pharmacokinetics of oxazepam

Six healthy volunteers received oxazepam 15 mg i.v. and orally at an interval of at least one week. The kinetic variables of i.v. oxazepam were: elimination half-life (t1/2 beta) 6.7 h, total clearance (CL) 1.07 ml.min-1.kg-1, volume of distribution (Vc) 0.27 l.kg-1 (0.21-0.49) and volume of distribution at steady-state (Vss) 0.59 l.kg-1. The intravenous disposition of unbound oxazepam was characterized by a clearance of 22.5 ml.min-1.kg-1 and a distribution volume of 12.3 l.kg-1. After oral oxazepam the peak plasma level was reached in 1.7 to 2.8 h. The plasma t1/2 beta at 5.8 h was not significantly different from the i.v. value. Absorption was almost complete, with a bioavailability of 92.8%. Urinary recovery was 80.0 and 71.4% of the dose after intravenous and oral administration, respectively. Renal clearance (CLR) of the glucuronide metabolite was 1.10 ml.min-1.kg-1 (0.98-1.52). Oxazepam was extensively bound to plasma protein with a free fraction of 4.5%.