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

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Abstract
Kinetic parameters were derived from trimipramine and demethyltrimipramine plasma concentrations after administration of i.v. (12.5 mg) and oral (50 mg) trimipramine in 9 subjects. Elimination t1/2 [half-life] after i.v. dosing was (mean .+-. SE) 23 .+-. 1.9 h. Volume of distribution by the area method was 30.9 .+-. 3.5 l/kg and total metabolic clearance was 15.9 .+-. 1.5 ml/min per kg. Plasma protein binding of trimipramine, as determined by equilibrium dialysis, averaged 94.9%, with a range of 93.8-96.4%. Peak plasma level attained was 28.2 .+-. 4.4 ng/ml at 3.1 .+-. 0.6 h after oral dosing. Absolute bioavailability was 41.4 .+-. 4.4% (range of 17.8-62.7%). Evidently, trimipramine has incomplete and variable systemic availability, it is more highly protein bound than other tricyclic antidepressants, and on the basis of its elimination t1/2, it could be administered on a twice-daily basis without marked interdose fluctuations in plasma levels.

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