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 24h. 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.
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Burch, J.E., Shaw, D.M., Michalakeas, A. et al. Time course of plasma drug levels during once-daily oral administration of clomipramine. Psychopharmacology 77, 344–347 (1982). https://doi.org/10.1007/BF00432768
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DOI: https://doi.org/10.1007/BF00432768