PERSISTENT IMPAIRMENT OF CLOMIPRAMINE DEMETHYLATION IN RECENTLY DETOXIFIED ALCOHOLIC PATIENTS

The purpose of the present study was to investigate whether the metabo lism of clomipramine is altered by chronic alcohol drinking. Eleven re cently detoxified alcoholic patients were included (experimental group EG) and compared to a reference group of patients with no history of alcoholism (reference group RG, n = 102). Blood concentrations of clom ipramine and its metabolites were measured as part of the routine drug monitoring program. Clearances were estimated from trough concentrati ons, according to a model developed previously. Results indicate stron g inhibition of demethylation clearance in group EG, when compared to group RG (median values 9.9 and 24.2 L/h), with significant increase o f the clomipramine to desmethylclomipramine ratio (median values 1.00 and 0.36). No difference was found for hydroxylation. In addition, hig h correlation is observed between hydroxylation and demethylation clea rances in group EG (Spearman r(s) = 0.82), but not in reference group RG (r(s) = 0.29). Follow-up data indicate that impairment of demethyla tion capacity can persist for several weeks or months after withdrawal from alcohol. The interest of calculating clomipramine to desmethylcl omipramine ratios during routine drug monitoring is emphasized, values of 1 or larger often being associated with liver disease and/or alcoh ol-related problems.