title: Trimipramine kinetics and absolute bioavailability: use of gas-liquid chromatography with nitrogen-phosphorus detection.
abstract: 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 t1/2 after intravenous dosing was (mean +/- SE) 23 +/- 1.9 hr. 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/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 t1/2, that it could be administered on a twice-daily basis without marked interdose fluctuations in plasma levels.
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001682:Biological Availability; D002849:Chromatography, Gas; D002997:Clomipramine / Q000097:blood; D003984:Dibenzazepines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D014299:Trimipramine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000031:analogs & derivatives
chemical_list: D003984:Dibenzazepines; D014299:Trimipramine; C040606:desmethyltrimipramine; D002997:Clomipramine