氟伐他汀80毫克缓释片介绍（刘承云教授201008）（修）课件.ppt

这是氟伐他汀缓释片80mg与速释胶囊40mg的药代动力学曲线对比。可以看到， 与速释胶囊比较，缓释片的吸收明显减慢（Tmax), 达峰浓度（Cmax）缓释片是速释胶囊的1/4。 缓释片的吸收速率较速释胶囊减慢了50%（Cmax/AUC0-t 0.19 vs.0.37) , 系统暴露减少50%（AUC0-t (ng*h/ml) 564 vs.1165）。 Lescol? XL was absorbed more slowly than the immediate-release formulation as measured by tmax. The maximum concentration observed post dose (Cmax) was about 4-fold lower for Lescol? XL compared with Lescol? IR. Exposure to fluvastatin as measured by AUC0-t was about 2-fold lower with the extended-release formulation compared with Lescol? IR. These effects are probably due to the longer exposure of the drug to the liver in Lescol? XL, without saturating first-pass metabolism. 本试验为研究食物对氟伐他汀缓释片药代动力学的影响。 当他汀与食物同服时（特别是高脂饮食），会产生“剂量倾倒“现象，即药物过度快速的吸收，产生高的需要浓度，不良反应的发生机会增加。 本研究采用标准膳食，即脂肪的含量30%的总卡路里。研究餐时和餐后2.5小时服用缓释片的药代曲线，时间的选择与临床的他汀服用时间相似（空腹或睡前）。 结果如图所示，食物不影响氟伐他汀缓释片的药代动力学曲线 所以氟伐他汀可以与食物同服。 Dose dumping when co-administered with food is a major concern with extended-release formulations (particularly with meals of high-fat content). The potential for such an interaction between Lescol? XL 80 mg and food has therefore been investigated in two studies. Fluvastatin ER 80 mg was administered under fed or 2.5-hour post-prandial conditions to mimic likely clinical use (i.e. administration with the evening meal or at bedtime). The meal was standardised, and comprised a fat content of 30% as total calories. Overall, administration with food had no clinically relevant effect on the pharmacokinetics of fluvastatin ER. In a separate study (data not shown) the effect of a high-fat breakfast (at least 50% fat as total calories) on the pharmacokinetic profile of fluvastatin ER were examined. Compared with the fasting state, the high-fat meal increased the systemic exposure of fluvastatin by approximately 50%. However, maximum serum fluvastatin concentrations (mean 183?ng/ml) were still around 6-fold lower than those observed with an identical dosage of the immediate-release formulation. The overall conclu