Trimipramine kinetics and absolute bioavailability: Use of gas‐liquid chromatography with nitrogen‐phosphorus detection

Kinetic parameters were derived from trimipramine and desmethyltrimipramine plasma concentrations after administration of intravenous (12.5 mg) and oral (50 mg) trimipramine in nine subjects. Elimination t 1/2 after intravenous dosing was (mean ±SE) 23 ± 1.9 hr. Volume of distribution by the area method was 30.9 ±3.5 I/kg and total metabolic clearance was 15.9 ± 1.5 ml/min/kg. Plasma protein binding of trimipramine, as determined by equilibrium dialysis, averaged 94.9%, with a range of 93.8% to 96.4%. Peak plasma level attained was 28.2 ± 4.4 ng/ml at 3.1 ± 0.6 hr after oral dosing. Absolute bioavailability was 41.4% ± 4.4% (range of 17.8% to 62.7%). These data indicate that trimipramine has incomplete and variable systemic availability, that it is more highly protein bound than other tricyclic antidepressants, and, on the basis of its elimination t 1/2 , that it could be administered on a twice‐daily basis without marked interdose fluctuations in plasma levels. Clinical Pharmacology and Therapeutics (1984) 35, 348–353; doi: 10.1038/clpt.1984.42