Effects of Multiple Doses of Clarithromycin on the Pharmacokinetics of Laropiprant in Healthy Subjects
| Autor: | Jules I. Schwartz, John A. Wagner, Larissa Wenning, Rajesh Desai, Patricia Jumes, Wen-Lin Luo, Ying-Hong Wang, Eseng Lai |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Pharmacology
Protein synthesis inhibitor business.industry Cmax Antagonist General Medicine Drug interaction chemistry.chemical_compound chemistry Pharmacokinetics Clarithromycin Medicine Pharmacology (medical) Cardiology and Cardiovascular Medicine business Laropiprant medicine.drug Antibacterial agent |
| Zdroj: | Cardiovascular Therapeutics. 29:140-145 |
| ISSN: | 1755-5914 |
| Popis: | Laropiprant is a selective antagonist of the prostaglandin D2 receptor subtype 1, and is primarily eliminated via glucuronidation with a minor contribution from oxidative metabolism via CYP3A. The effects of multiple oral doses of clarithromycin on the pharmacokinetics of laropiprant were investigated in an open-labeled, randomized, 2-period cross-over study. A single oral dose of 40 mg laropiprant was administered alone or coadministered with 500 mg clarithromycin b.i.d. on Day 5 of a 7-day clarithromycin regimen. Geometric mean ratios (90% confidence intervals) for AUC0-∞ and Cmax of laropiprant in the presence versus absence of clarithromycin were 1.39 (1.19, 1.62) and 1.46 (1.17, 1.80), respectively. No statistically significant differences were observed in Tmax (P= 0.543) or apparent terminal half-life (P= 0.502) of laropiprant, which implies that the effect of clarithromycin on laropiprant is largely a first-pass rather than a systemic effect. The results of this study suggest that laropiprant is not a sensitive CYP3A substrate, and strong CYP3A inhibitors like clarithromycin are not expected to have a clinically meaningful impact on the pharmacokinetics of laropiprant. |
| Databáze: | OpenAIRE |
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