New Compounds as Potential DDI Victims

If the enzyme is subject to genetic polymorphism with an allele coding for a nonfunctional enzyme, the comparison of the pharmacokinetics of a dmg in subjects homozygous for the null allele to control subjects can yield a value for L- 

If one assumes that an inhibitor or inactivator, selective for an enzyme in question, can be dosed in such a manner so as to completely abolish the activity of an enzyme in vivo, then a clinical DDI study using that inhibitor can be used to estimate for that enzyme for the victim drug. 

Using data from a human radiolabel ADME study in which metabolic pathways are fully delineated, in combination with in vitro data that identifies which enzymes are responsible for which metabolic pathways, values of can be estimated. 

However, in early drug research, such data are not available. Thus, even more crude estimates must be used for fcL- Since most of the important DDI are mediated by effects on the GYP enzymes, a three-tiered approach can be used to gain an assessment former for prediction of DDI for the new compound as a victim of DDI  

What fraction of clearance will occur via excretion of unchanged drug (i.e., renal or biliary) versus metabolism  

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