Characterization of desmethylimipramine 2-hydroxylation in human foetal and adult liver microsomes.

The rate of formation of 2-hydroxydesmethylimipramine was studied in microsomes from four human foetal and adult livers. The concentrations of desmethylimipramine ranged between 5 and 100 microM. The concentration of 2-hydroxydesmethylimipramine was measured by high pressure liquid chromatography with fluorescence detection. The kinetic parameters (Vmax and Km) were measured by Eadie-Hofstee plot. The Vmax (mean +/- S.E.M.) was 2.80 +/- 0.84 (foetal liver) and 73.1 +/- 11.6 (adult liver) pmol X min.-1 X mg-1. The corresponding values for Km (microM) were 36.3 +/- 6.5 (foetal liver) and 14.1 +/- 1.3 (adult liver). Both parameters were significantly different in foetal and in adult liver. The inhibitory effects of thioridazine, metoprolol, carbamazepine and cimetidine on the 2-hydroxylation of desmethylimipramine were studied in the foetal liver microsomes. Thioridazine and carbamazepine were the most powerful inhibitors.