科研之友
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摘要
Objectives Clopidogrel, a thienopyridine antiplatelet agent, is a poor aqueous soluble compound and a P-glycoprotein (P-gp) efflux pump substrate. These two factors are responsible for its incomplete intestinal absorption. In this study, we have attempted to enhance the absorption of clopidogrel by improving its solubility and by inhibiting intestinal P-gp activity. Methods Solubility enhancement was achieved by preparing solid dispersions. Quinidine and naringin were selected as P-gp inhibitors, whilst tartaric acid was selected as the intestinal absorption enhancer. Absorption studies were performed using the everted gut sac model prepared from rat jejunum. The determination of clopidogrel was performed by high performance liquid chromatography. Key findings We noticed an enhancement of clopidogrel absorption by improving its solubility or by inhibiting the P-gp activity. The greatest results were obtained for solid dispersions in the presence of P-gp inhibitors at their highest concentrations, with an absorption improvement of 3.41-and 3.91-fold for naringin (15 mg/ kg) and quinidine (200 mm), respectively. However, no clopidogrel absorption enhancement occurred in the presence of tartaric acid. Conclusions Naringin, a natural compound which has no undesirable side effects as comparedwith quinidine, could be used as a pharmaceutical excipient in the presence of clopidogrel solid dispersions to increase clopidogrel intestinal absorption and therefore its oral bioavailability.
- 出版日期2012-4
