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

Darrell R. Abernethy, David J. Greenblatt, Richard I. Shader

Research output: Contribution to journalArticlepeer-review

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 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 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 t 1 2, that it could be administered on a twice-daily basis without marked interdose fluctuations in plasma levels.

Original languageEnglish (US)
Pages (from-to)348-353
Number of pages6
JournalClinical pharmacology and therapeutics
Volume35
Issue number3
DOIs
StatePublished - Mar 1984

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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