Pharmacokinetics of fosinoprilat in Chinese and whites after intravenous administration.

Abstract

The pharmacokinetics of fosinoprilat was studied in 12 healthy Chinese men after a 7.5 mg intravenous dose of fosinoprilat. The data were compared with those from an earlier study using the same protocol in nine healthy white men. Blood and urine samples were obtained before and at various time intervals after fosinoprilat administration up to 24 hours and 48 hours, respectively. Pharmacokinetic parameters were calculated by fitting the plasma or serum concentrations to a three-compartment model. The total clearance (Clt), renal clearance (ClT), and nonrenal clearance (ClNR) were significantly lower in Chinese (16.29 +/- 6.92, 6.85 +/- 2.97, and 9.44 +/- 5.08 mL.hr-1.kg-1) than those obtained in whites (29.88 +/- 6.36, 13.55 +/- 3.45, and 16.33 +/- 5.07 mL.hr-1.kg-1). The Chinese subjects had a significantly lower volume of distribution (Vc [volume of distribution of central compartment] and Vdss [volume of distribution at steady state]) (29.38 +/- 21.12 and 73.67 +/- 40.20 mL/kg) than white men (58.14 +/- 15.01 and 152.49 +/- 24.89 mL/kg). The Chinese men also had a shorter elimination half-life than whites, although not statistically significant. The respective half-lives in Chinese and whites were 5.51 +/- 1.53 and 8.24 +/- 1.99 hours. The significant differences in ClNR and ClR may be related to lower liver elimination function and lower kidney excretory function, respectively. Plasma protein binding may contribute to part of the difference in the volume of distribution. Chinese men have smaller volume of distribution and clearances of fosinoprilat after intravenous administration compared with white men. The cumulative urine excretion of fosinoprilat was not different between Chinese and whites. Chinese may require a lower fosinoprilat dosage to obtain plasma concentrations similar to whites after intravenous administration. However, since a relatively high variation was found in fosinopril oral absorption, the oral dosage of fosinopril for Chinese and whites may not be different. Further study is obviously needed to elucidate whether the pharmacodynamic effect may be different between Chinese and whites.