Prediction of human drug clearance from animal data: application of the rule of exponents and 'fu Corrected Intercept Method' (FCIM).
The objective of this study is to evaluate the predictive performance of the rule of exponents (ROE) and 'fu Corrected Intercept Method' (FCIM) for the human drug clearance. Different classes of drugs such as extensively metabolized, renally excreted, renally secreted, and biliary excreted drugs were used in this analysis. The results of the study indicated that both these methods under given conditions are extremely useful for the prediction of human drug clearance. There are certain situations under which one of these methods is more suited than the other method. Overall, it appears that a rational use of FCIM and the ROE can help a great deal in obtaining a better estimate of the human drug clearance for a wide variety of drugs. The advantages and disadvantages of these two methods are also discussed.
Mahmood
Iftekhar
I
Clinical Pharmacology and Toxicology Branch (HFD-579), Office of Drug Evaluation VI, Center for Drug Evaluation and Research, Food & Drug Administration, Woodmont Office Center II, Rockville, Maryland 20852, USA. Mahmoodi@CDER.FDA.GOV
D000818:Animals; D016208:Databases, Factual; D004285:Dogs; D000882:Haplorhini; D006801:Humans; D008657:Metabolic Clearance Rate / Q000502:physiology; D051379:Mice; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011237:Predictive Value of Tests; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013678:Technology, Pharmaceutical / Q000379:methods*
D004364:Pharmaceutical Preparations