Fosinopril: Pharmacokinetics and pharmacodynamics in Chinese subjects

This study examined the pharmacokinetics and pharmacodynamics of fosinopril (IV and oral) in Chinese subjects to determine whether they were different from a group of somewhat heavier and older Western control subjects previously published using the same methods. It was an open-label, randomized, balanced, two-way crossover study comparing oral and IV pharmacokinetics in 12 healthy Chinese subjects in a clinic in Taiwan. Each subject received 10 mg of oral fosinopril or 7.5 mg of IV fosinoprilat in a randomized sequence with sampling for fosinoprilat concentrations over 48 hours. Standard pharmacokinetics, including AUC, C(max), T(max), T( 1/2 ), V(ss), bioavailability, total clearance, and renal and nonrenal clearance, were determined as well as pharmacodynamic effects on angiotensin-converting enzyme (ACE) activity. Following oral administration of 10 mg fosinopril, AUC(0-T) and AUC(inf) were 1556 ± 586 ng · hr/mL and 1636 ± 620 ng · hr/mL, respectively; T( 1/2 ) was 17.4 ± 11.4 hr; C(max) was 183.4 ± 59.4 ng/mL; and median T(max) was 4.0 hr, with ≥ 99% protein binding. Following IV administration of 7.5 mg fosinoprilat, AUC(0-T) and AUC(inf) were 7727 ± 2638 ng · hr/mL and 7816 ± 2693 ng · hr/mL, respectively; T( 1/2 0) was 13.0 ± 5.2 hr; and median T(max) was 4.0 hr, with 99.5% ± 0.22% protein binding and a V(ss) of 5850 ± 2780 mL. Bioavailability was 22.3% ± 7.9%. Percent urinary excretion was 7.6% ± 2.6% after oral dosing and 42.6% ± 6.1% after IV dosing. After IV, dosing total clearance was 1088 ± 439 mL/hr, renal clearance was 472 ± 213 mL/hr, and nonrenal clearance was 617 ± 246 mL/hr. ACE inhibition was essentially complete through 12 hours and markedly reduced through 24 hours. Compared to a somewhat heavier and older previously reported control group, pharmacokinetic values were similar except for a slightly lower AUC and total clearance in Chinese and a statistically significantly lower nonrenal clearance. Pharmacodynamic effects on ACE activity were essentially identical. There is no reason to expect significant differences in fosinopril dosing or effect in a Chinese population compared to a Western population.