INFLUENCE OF FOOD ON THE PHARMACOKINETICS OF PERINDOPRIL AND THE TIME COURSE OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION IN SERUM

Food has been shown to reduce the bioavailability of the angiotensin-converting enzyme inhibitor captopril, but not the bioavailability of inhibitors administered as ester prodrugs. Perindopril is the ester pro-drug of the angiotensin-converting enzyme inhibitor perindoprilat. The influence of food on the pharmacokinetics of perindopril (4 mg administered orally) and the time course of angiotensin-converting enzyme inhibition in serum was studied in a randomized crossover short-term study of 12 healthy subjects. Food significantly decreased the relative availability of perindoprilat by 35% ± 42%, the fractional urinary excretion of perindoprilat from 19% ± 7% to 13% ± 4% (p < 0.05), and the partial metabolic clearance of perindopril to perindoprilat from 102 ± 57 ml · min-1 to 72 ± 32 ml · min-1 (p < 0.05). These changes were associated with a significant decrease in the area under the percent angiotensin-converting enzyme inhibition-versus-time curve by 15% (p < 0.05). Food did not alter the total amount of drug recovered in urine as perindopril and its metabolites, and it did not alter perindoprilat renal clearance. We concluded that food alters the conversion of perindopril to its active metabolite perindoprilat after single-dose administration of perindopril. © 1990.