Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2486202 | Journal of Pharmaceutical Sciences | 2011 | 11 Pages |
Abstract
In this study, an examination of the potential effect of lipids on the firstâpass metabolism of anethol trithione (ATT) was investigated. ATT is metabolized rapidly and extensively in liver into 4âhydroxyâanethole trithione (ATX), which was confirmed using the rat intestinal perfusion with the mesenteric cannulation model. Male Sprague-Dawley rats were orally administered of the lipidâbased formulations (prepared by medium chain triglycerides (MCT)), the cyclodextrin formulation and the suspension formulation, respectively. For 6.75Â mg/kg groups, ATX/ATT area under the plasma concentrationâtime curve (AUC) ratio decreased by 87% and 76% after administration of the MCTâbased formulations and the cyclodextrin formulation, when compared with the suspension formulation (p < 0.05), respectively; for 2.25Â mg/kg groups, it decreased by 53% in the MCT group when compared with the cyclodextrin group (p < 0.05). The saturation of preâsystem metabolism of ATT was observed after administration of the MCTâbased formulations and the cyclodextrin formulation, likely as a result of enhanced absorption and therefore presentation of higher drug concentrations to liver, when compared with the suspension formulation. A trend toward lower systemic metabolite to parent ratios was evident after administration of the lipid formulations, when compared with the cyclodextrin formulation; however, this was not statistically significant. Further studies on the potential for lipids to inhibit hepatic metabolism are therefore warranted. © 2011 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 100:5048-5058, 2011
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Drug Discovery
Authors
HongâZhen Yu, SiâFei Han, Ping Li, ChunâLiu Zhu, XinâXin Zhang, Li Gan, Yong Gan,