First-pass metabolism of imipramine and desipramine: impact of the sparteine oxidation phenotype.

Four rapid extensive metabolizers (EM), four slow EM, and three poor metabolizers (PM) of sparteine were given single intravenous doses of 50 mg imipramine and desipramine. All subjects had previously taken single oral doses (100 mg) of imipramine and desipramine. The first-pass metabolism of imipramine and desipramine ranged from 23% to 73% and 0% to 48%, respectively, and was more pronounced for both drugs in EM than in poor metabolizers. The study suggested saturable 2-hydroxylation of imipramine and desipramine during the first-pass through the liver, especially in EM.