First-pass metabolism of imipramine in man.

The systemic availability of orally administered imipramine (IP) varied from 29 to 77% in 4 subjects. The decrease in availability was due to an excess in metabolism after oral administration. This first-pass metabolism did not correlate with plasma half-life, apparent clearance, or the rate of metabolite excretion in urine. There was close correlation with the excess in formation of demethylated metabolites after oral administration, which suggests that the first-pass metabolism is mediated by demethylation, but does not correlate to the total rate of demethylation.