کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2549946 | 1124533 | 2006 | 11 صفحه PDF | دانلود رایگان |
IntroductionThis study was conducted to compare and contrast published in vitro intrinsic clearance values reported for compounds from different laboratories and the predictivity of these data to project in vivo clearance.MethodsA total of 103 compounds were selected for investigation and an exhaustive literature search was conducted to identify in vitro intrinsic clearance (CL,i) values for comparative purposes. The simple well-stirred model was used to predict in vivo clearance using these in vitro intrinsic clearance values.ResultsData were available in the literature for < 10% of the compounds of interest in rat, dog, monkey, or human S9, as well as < 10% for dog or monkey microsomes or hepatocytes. Therefore, this comparative exercise was limited to rat and human microsomes and hepatocytes. Examination of the available CL,i values indicated a substantial (up to 100 s-fold) variation in values reported in the literature; this variability translated into substantial variation in predicted in vivo clearance.DiscussionThe literature paucity and variability described here demonstrate the importance of generating experimentally consistent de novo CL,i data for the purpose of method validation or in vitro–in vivo scaling.
Journal: Journal of Pharmacological and Toxicological Methods - Volume 53, Issue 2, March–April 2006, Pages 106–116