Fosinopril: pharmacokinetics and pharmacodynamics in Chinese subjects.
This study examined thepharmacokinetics and pharmacodynamics of fosinopril (IVand 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 fosinoprilatin a randomized sequence with sampling for fosinoprilat concentrations over 48 hours. Standard pharmacokinetics, including AUC, Cmax Tmax, T 1/2, Vss, 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, AUC0-T and AUCinf were 1,556 +/- 586 ng x hr/mL and 1,636 +/- 620 ng x hr/mL, respectively; T 1/2 was 17.4 +/- 11.4 hr; Cmax was 183.4 +/- 59.4 ng/mL; and median Tmax was 4.0 hr, with > 99% protein binding. Following IV administration of 7.5 mg fosinoprilat, AUC0-T and AUCinf were 7,727 +/- 2,638 ng x hr/mL and 7,816 +/- 2,693 ng x hr/mL, respectively; T 1/2 was 13.0 +/- 5.2 hr; and median Tmax was 4.0 hr, with 99.5% +/- 0.22% protein binding and a Vss of 5,850 +/- 2,780 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 1,088 +/- 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.
Ding
P Y
PY
Division of Cardiology, Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan, ROC.
Chu
K M
KM
Hu
O Y
OY
Huang
G M
GM
Jeng
J J
JJ
Chang
A
A
Delaney
C L
CL
MacAskill
M
M
Yang
B C
BC
Jemal
M
M
Smith
R
R
Liao
W C
WC
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000652:urine; D019540:Area Under Curve; D044466:Asian People; D001682:Biological Availability; D016001:Confidence Intervals; D018592:Cross-Over Studies; D017328:Fosinopril / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000652:urine; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A; D017328:Fosinopril