The Clinical Pharmacokinetics of Quinapril

Abstract

Quinapril (Q) and quinaprilat (QT) pharmacokinetics are dose pro portional following single oral 2.5- to 80-mg Q doses. Q absorption and hy drolysis to QT is rapid with peak Q and QT concentrations occurring one and two hours postdose, respectively. Peak plasma QT concentrations were approximately fourfold higher than those of Q (923 vs 207 ng/mL follow ing 40-mg Q). Dose-proportional QT area under the curve and dose-inde pendent percent of dose excreted in urine as QT demonstrate that the ex tent of Q conversion to QT is con stant over the dose range studied. Q and QT were eliminated from plasma with apparent half-lives of 0.8 and 1.9 hours and apparent plasma clear ances of 1,850 and 220 mL/min, re spectively, over the 2.5- to 80-mg dose range. Following oral 14C-Q, 61% and 37% of radiolabel was recovered in urine and feces, respectively. Q plus QT accounted for 46% of radioactiv ity circulating in plasma and 56% of that excreted in urine. Metabolism to compounds other than QT is not extensive. Two diketo piperazine metabolites of Q have been identified in plasma and urine, with approximately 6% of an admin istered dose excreted in urine as each of these metabolites. Peak plasma concentrations of these metabolites are similar to that of Q, and each is eliminated rapidly with a half-life of approximately one hour. Urinary ex cretion profiles indicate the presence of other minor metabolites. In summary, the absorption of Q and conversion to QT is rapid and dose-proportional, subsequent clear ance of both Q and QT is independ ent of dose, and metabolism to compounds other than QT is not ex tensive.