title: Time course of plasma drug levels during once-daily oral administration of clomipramine.
abstract: Fourteen depressed in-patients were treated with 150 mg clomipramine (CLO) daily, given as one oral dose. Using a gas-chromatographic method, concentrations of CLO and desmethyl clomipramine (DMCLO) were determined in plasma samples taken at frequent intervals during 24 h. The plasma level of each compound 12 h after the dose correlated well with the average value in the same patient, calculated over the whole 24-h period. Levels at other times gave poorer correlations, and at 24 h it was particularly poor. Plasma DMCLO concentrations were usually maximum 4-6 h after the dose. The ratios of maximum to minimum levels averaged only 1.31 +/- 0.15 SD. Peak CLO levels occurred 3 or 4 h after the dose. Maximum; minimum ratios averaged 2.72 +/- 0.73 SD, contrasting with the much smaller fluctuations of plasma nortriptyline (NT) levels observed in patients given this drug once daily. The difference is not due to a shorter half-life of CLO, but to the absorption and/or distribution behaviour of the two drugs. Although not fully understood, this difference between tertiary and secondary amines appears to hold generally among the tricyclic antidepressants.
mesh_terms: D000284:Administration, Oral; D002997:Clomipramine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood*; D006801:Humans; D013997:Time Factors
chemical_list: C012273:desmethylclomipramine; D002997:Clomipramine