TY - JOUR
T1 - Trimipramine kinetics and absolute bioavailability
T2 - Use of gas-liquid chromatography with nitrogen-phosphorus detection
AU - Abernethy, Darrell R.
AU - Greenblatt, David J.
AU - Shader, Richard I.
PY - 1984/3
Y1 - 1984/3
N2 - 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.
AB - 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.
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U2 - 10.1038/clpt.1984.42
DO - 10.1038/clpt.1984.42
M3 - Article
C2 - 6697642
AN - SCOPUS:0021369281
SN - 0009-9236
VL - 35
SP - 348
EP - 353
JO - Clinical pharmacology and therapeutics
JF - Clinical pharmacology and therapeutics
IS - 3
ER -