| Autor: |
Modi, Nishit B., Novotny, William, Reimann, James D., Cannon, Christopher P., Braunwauld, Eugene |
| Zdroj: |
Journal of Clinical Pharmacology; Jul1999, Vol. 39 Issue 7, p675-684, 10p |
| Abstrakt: |
Sibrafiban is a double prodrug that is converted to the inactive single prodrug and to the active IIb/IIIa antagonist following oral administration. Pharmacokinetics (PK) and pharmacodynamics (PD) of oral sibrafiban and its metabolites were evaluated in patients postacute coronary syndrome receiving once-or twice-daily sibrafiban for up to 28 days at several dose levels. Mean peak concentrations of sibrafiban were < 5 ng/mL. Peak single prodrug concentrations occurred 1.7 ± 1.0 (mean ± SD) hours after sibrafiban dosing. Total apparent plasma clearance of the single prodrug was 40 ± 15 L/h, and the elimination half-life was 2.3 ± 0.8 hours. Mean values of the steady-state pharmacokinetics for total concentrations of the active drug over all doses were: time to peak plasma concentration, 5.0 ± 1.7 hours; apparent clearance, 13.9 ± 3.9 L/h; and half-life, 11.0 ± 2.8 hours. Once-daily dosing resulted in high peak-trough excursions in active drug concentrations: trough concentrations were 21% ± 6% of peak. Twice-daily dosing resulted in an AUC for the active drug on Day 28 that was 168% ± 36% of that on Day 1, and steady-state trough concentrations were 54% ± 10% of peak with sustained inhibition of platelet aggregation. Dose-adjusted steady-state active drug concentrations increased with increasing age and with decreasing renal function and body weight. [ABSTRACT FROM PUBLISHER] |
| Databáze: |
Complementary Index |
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