Pharmacokinetics and pharmacodynamics of multiple oral doses of MK-0591, a 5-lipoxygenase—activating protein inhibitor
| Autor: | Beth Friedman, Aimee Dallob, Sumiko Shingo, Charles Lin, Anne Van Hecken, Inge De Lepeleire, Wesley Tanaka, Paul J. De Schepper, Arturo Porras, Marken Depré |
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| Rok vydání: | 1994 |
| Předmět: |
Adult
Male Indoles Leukotriene B4 5-Lipoxygenase-Activating Proteins Administration Oral Pharmacology chemistry.chemical_compound Double-Blind Method Pharmacokinetics Reference Values Oral administration Blood plasma Humans Testosterone Pharmacology (medical) Lipoxygenase Inhibitors Whole blood Analysis of Variance Leukotriene E4 Membrane Proteins Respiratory Function Tests chemistry Pharmacodynamics Quinolines Leukotriene Antagonists Carrier Proteins Ex vivo |
| Zdroj: | Clinical Pharmacology and Therapeutics. 56:22-30 |
| ISSN: | 1532-6535 0009-9236 |
| DOI: | 10.1038/clpt.1994.96 |
| Popis: | 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 B4 biosynthesis ex vivo in ionophore (A23187)-stimulated whole blood and leukotriene E4 levels in urine were determined. Leukotriene B4 production was inhibited up to 90% of baseline for 12 hours after administration at the highest dose. The degree of leukotriene B4 inhibition ex vivo in whole blood significantly correlated with plasma MK-0591 concentrations (0 to 1500 ng/ml; r = 0.73). Urinary leukotriene E4 was 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: | OpenAIRE |
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