PHARMACOKINETICS OF FOSINOPRILAT IN CHINESE AND WHITES AFTER INTRAVENOUS ADMINISTRATION

The pharmacokinetics of fosinoprilat was studied in 12 healthy Chinese men after a 7.5 mg intravenous dose of fosinoprilat. The data were co mpared with those from an earlier study using the same protocol in nin e healthy white men. Blood and urine samples were obtained before and at various time intervals after fosinoprilat administration up to 24 h ours and 48 hours, respectively. Pharmacokinetic parameters were calcu lated by fitting the plasma or serum concentrations to a three-compart ment model. The total clearance (Cl-t), renal clearance (Cl-T), and no nrenal clearance (Cl-NR) were significantly lower in Chinese (16.29 +/ - 6.92, 6.85 +/- 2.97, and 9.44 +/- 5.08 mL.hr(-1).kg(-1)). The Chines e subjects had a significantly lower volume of distribution (V-c [volu me of distribution of central compartment] and Vd(ss) [volume of distr ibution at steady state]) (29.38 +/- 21.12 and 73.67 +/- 40.20 mL/kg) than white men (58.14 +/- 15.01 and 152.01 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 +/- 4.99 hours. The si gnificant differences in Cl-NR and Cl-R 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 t he volume of distribution. Chinese men have smaller volume of distribu tion and clearances of fosinoprilat after intravenous administration c ompared with white men. The cumulative urine excretion of fosinoprilat was not different between Chinese and whites. Chinese may require a l ower fosinoprilat dosage to obtain plasma concentrations similar to wh ites after intravenous administration. However, since a relatively hig h variation was found in fosinopril oral absorption, the oral dosage o f fosinopril in Chinese and whites may not be different. Further study is obviously needed to elucidate whether the pharmacodynamic effect m ay be different between Chinese and whites.