Fosinopril: Pharmacokinetics and pharmacodynamics in Chinese subjects

Philip Y.A. Ding, Kai Ming Chu, Oliver Yoa Pu Hu, Giang Ming Huang, Jing Jen Jeng, Audrey Chang, Carol L. Delaney, Maynard MacAskill, B. C. Yang, Mohammed Jemal, Robert Smith, Wei Chi Liao

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Abstract

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.

Original languageEnglish
Pages (from-to)155-160
Number of pages6
JournalJournal of Clinical Pharmacology
Volume39
Issue number2
DOIs
Publication statusPublished - Feb 13 1999
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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  • Cite this

    Ding, P. Y. A., Chu, K. M., Hu, O. Y. P., Huang, G. M., Jeng, J. J., Chang, A., Delaney, C. L., MacAskill, M., Yang, B. C., Jemal, M., Smith, R., & Liao, W. C. (1999). Fosinopril: Pharmacokinetics and pharmacodynamics in Chinese subjects. Journal of Clinical Pharmacology, 39(2), 155-160. https://doi.org/10.1177/00912709922007705