The pharmacokinetics of clomipramine and desmethylclomipramine in dogs: parameter estimates following a single oral dose and 28 consecutive daily oral doses of clomipramine

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 Mras 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 1.3-2.3 h. Clinically significant differences between dogs and humans in the pharmacokinetics of oral clomipramine are discussed.