| Autor: |
Depré, Marken, Friedman, Beth, Van Hecken, Anne, De Lepeleire, Inge, Tanaka, Wesley, Dallob, Aimee, Shingo, Sumiko, Porras, Arturo, Lin, Charles, De Schepper, Paul J |
| Zdroj: |
Clinical Pharmacology & Therapeutics; July 1994, Vol. 56 Issue: 1 p22-30, 9p |
| Abstrakt: |
The pharmacodynamics, kinetics, and tolerability of a new orally active 5-lipoxygenase inhibitor were evaluated in healthy male volunteers. MK-0591, 50, 125, and 250 mg every morning and 250 mg every 12 hours, was administered for 10 days. Leukotriene B4biosynthesis ex vivo in ionophore (A23187)-stimulated whole blood and leukotriene E4levels in urine were determined. Leukotriene B4production was inhibited up to 90% of baseline for 12 hours after administration at the highest dose. The degree of leukotriene B4inhibition ex vivo in whole blood significantly correlated with plasma MK-0591 concentrations (0 to 1500 ng/ml; r = 0.73). Urinary leukotriene E4was inhibited by >80% at 24 hours after administration for all dose levels. Pharmacokinetics of MK-0591 were linear, with a half-life of approximately 6 hours. Very little accumulation was seen after multiple dosing. MK-0591 had no effect on testosterone levels, and good tolerability was shown at all dose levels of MK-0591 administered for up to 10 days.Clinical Pharmacology and Therapeutics (1994) 56, 22–30; doi:10.1038/clpt.1994.96 |
| Databáze: |
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