Absolute Bioavailability and Effect of Food and Antacid on Diazepam Absorption from a Slow‐Release Preparation

Abstract

A series of healthy volunteers received a single 7.5‐mg intravenous dose of diazepam on one occasion and a single 15‐mg oral dose of slow‐release diazepam (DZ‐SR) on another occasion. Diazepam concentrations were measured by gas chromatography in multiple plasma samples drawn during seven days after each dose. Absorption of diazepam from DZ‐SR was slow, with mean ± S.E. peak concentrations attained at 3.8 ± 0.5 hours after dosage. Absolute bioavailability of DZ‐SR averaged 0.98 ± 0.06. In two other studies, diazepam absorption from DZ‐SR was evaluated when coadministered with a standard breakfast or with an antacid preparation (Maalox). Neither food nor antacid altered the rate of diazepam absorption and did not impair the completeness of absorption. Higher peak total plasma diazepam concentrations occurred in the postprandial as opposed to the fasting state, but this was an artifact of reduced protein binding (increased free fraction) due to fasting. Thus, diazepam absorption from DZ‐SR is slow and essentially complete.