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Trimipramine kinetics and absolute bioavailability: Use of gas‐liquid chromatography with nitrogen‐phosphorus detection
Author(s) -
Abernethy Darrell R,
Greenblatt David J,
Shader Richard I
Publication year - 1984
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1984.42
Subject(s) - chemistry , bioavailability , volume of distribution , pharmacokinetics , chromatography , dosing , pharmacology , medicine , organic chemistry
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