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The pharmacokinetics of clomipramine and desmethylclomipramine in dogs: parameter estimates following a single oral dose and 28 consecutive daily oral doses of clomipramine
Author(s) -
HEWSON C.J.,
CONLON P.D.,
LUESCHER U.A.,
BALL R.O.
Publication year - 1998
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1046/j.1365-2885.1998.00138.x
Subject(s) - clomipramine , pharmacokinetics , cmax , pharmacology , oral administration , dosing , chemistry , medicine
Clomipramine is a tricyclic antidepressant that has been recommended for the treatment of canine compulsive disorder. The pharmacokinetics of clomipramine in dogs have not been reported. This study describes the pharmacokinetics of clomipramine and its active metabolite, desmethylclomipramine, in six male dogs. Serial blood samples were collected following both a single oral dose of clomipramine (3 mg/kg) and 28 consecutive daily oral doses (3 mg/kg q 24 h). In addition, ‘peak’ and ‘trough’ samples were taken throughout the 28‐day dosing period. Plasma was assayed for total (free and protein‐bound) clomipramine and desmethylclomipramine, using gas‐chromatography with mass spectrometric detection. Various pharmacokinetic parameters were then determined. Following a single dose of clomipramine, time of maximum plasma concentration ( t max ) of clomipramine was 0.75–3.1 h, maximum plasma concentration ( C max ) was 16–310 ng/mL and elimination half‐life ( t 1/2el ) was 1.2–16 h; t max of desmethylclomipramine was 1.4–8.8 h, C max was 21–134 ng/mL and t 1/2el was 1.2–2.3 h. Following multiple dosing, there was a numeric increase in these parameters; t max of clomipramine was 3–8 h, C max was 43–222 ng/mL and t 1/2el was 1.2–16 h; t max of desmethylclomipramine was 1.4–8.8 h, C max was 21–134 ng/mL and t 1/2el was 1.2–2.3 h. Clinically significant differences between dogs and humans in the pharmacokinetics of oral clomipramine are discussed.