面临耐药性致病菌的逐年增加,新型抗菌药物亟待开发。众所周知,新药开发是一个艰难和复杂的过程。制定合理给药方案是药物开发的重要课题,而以制定抗菌药物的合理给药方案最富挑战性。近二十年来,便宜快捷的体外动力学实验和动物体内感染模型以及药效学数据处理方法不断完善,其价值在抗菌新药开发上被不断验证和肯定,弥补了临床试验所无法获得的信息。近十年来临床群体药代动力学模型和蒙地卡罗模拟结合临床前实验确定的靶值,致病菌 MIC 分布,利用电脑模拟比较不同给药方案的中靶率,已成为临床三期试验确定最佳给药方案行之有效的方法和针对耐药菌抗菌药物临床剂量再评价和进一步调整的科学依据。可以预期,在今后的抗菌素新药的开发上,人们将更有把握从临床前的实验数据来预计临床最佳给药方案,并优化临床试验的设计,达到既快速又经济的目的。
AIM:The inhibition of organic anion transporting polypeptide 1BI（OATPIB1）on the pharmacokinetics of rosuvastatin is ***,the effect of ursodeoxy- cholic acid（UDCA）on the kinetics of rosuvastatin in healthy voluntee...
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AIM:The inhibition of organic anion transporting polypeptide 1BI（OATPIB1）on the pharmacokinetics of rosuvastatin is ***,the effect of ursodeoxy- cholic acid（UDCA）on the kinetics of rosuvastatin in healthy volunteers is to be investigated. METHODS:The inhibition effect of long term use of UD- CA on rosuvastatin kinetics was studied in 12 subjects in a randomized,crossover *** subject received 500 mg UDCA once daily continuously for 14 days.A single oral dose of 20 mg rosuvastatin was given on study day 15 and 34 separated by 2 *** concentrations of ro- suvastatin were above the limits of quantitation for up to 72 h after dosing. RESULTS:UDCA significantly increased AUCand AUCof rosuvastatin to 146%±55%（P=0.008） and 167%±73%（P=0.004）compared with those of the control group and CL/F decreased 75%±19%（P= 0.003）.The results confirmed the in vitro study that UD- CA inhibited OATP1B1 activity via hepatic nuclear factor la（HNFIa）. CONCLUSION:Inhibition of HNF1 a and hepatic uptake may have consequences on clinic outcomes of drugs like rosuvastatin mainly excreted by hepatobiliary system.
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