| Autor: |
Fujino, Hideki, Shimada, Syunsuke, Yamada, Iwao, Hirano, Masaru, Tsunenari, Yoshihiko, Kojima, Junji |
| Předmět: |
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| Zdroj: |
Drug Research / Arzneimittel-Forschung (Editio Cantor Verlag fur Medizin und Naturwissenschaften); Oct2003, Vol. 53 Issue 10, p701, 7p |
| Abstrakt: |
To gain a better understanding of the mechanism of drug-drug interaction between fibrates and statins, several in vitro experiments were performed. On coincubation with several fibrates, pitavastatin (CAS 147526-32-7) did not displace fibrates from their protein binding in human plasma. The presence of gemfibrozil (CAS 25812-30-0) inhibited the metabolism of statins (cerivastatin (CAS 145599-86-6) and atorvastatin (CAS 134523-00-5)) remarkably. However, the increase of the unchanged form was fairly small for pitavastatin. The metabolic profile of gemfibrozil was also investigated. The cytochrome P (CYP) enzyme CYP2C9 plays a major role in the metabolism of gemfibrozil. Gemfibrozil showed a high affinity for CYP enzymes and a relatively high metabolism velocity. Moreover, several inhibitory effects of gemfibrozil on CYP-mediated metabolism were detected — in contrast to other fibrates. Although the mechanism of the drug-drug interaction was not completely clarified, it is suggested that the increase of plasma concentration caused by the co-administration of gemfibrozil and statins is at least partially due to the inhibition of the CYP-mediated metabolism. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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