Absolute bioavailability of imipramine: influence of food

Imipramine hydrochloride (IMI) was administered to 12 healthy volunteers on three occasions in random sequence: 12.5 mg IV, 50 mg orally after overnight fast, and 50 mg orally 30 min after eating a standardized breakfast. IMI concentrations were measured by gas-liquid chromatography using nitrogen-phosphorous detection and pharmacokinetic and bioavailability parameters determined by iterative nonlinear least-squares regression analysis. After IV administration, mean kinetic variables were: volume of distribution, 21.0 l/kg; total clearance, 12.8 ml/min per kg, and elimination half-life, 21. h. Mean absolute bioavailability of IMI in the fasting state was 43.6%. When IMI was administered immediately after the standardized meal, absolute bioavailability was 44.1%. After oral administration, the time to peak IMI level was not changed by concurrent food ingestion (2.8 vs 3.2 h after dosage), and the peak IMI concentration was no different (35 vs 30 ng/ml). Thus concurrent food ingestion has no effect on IMI absolute bioavailability, peak concentration attained after oral dosage, or the time to peak concentration.