Actually, metabolism has tons to do with whether or not a drug
gets to market. If a drug is metabolized to an inactive from--
"cleared"--too quickly, then you have to take it too often which
patients won't do. If a compound must be administered as a
conjugate or "pro-drug" to assure oral availability (gets to the
blood from the stomach), then the rate of activation needs to be
sufficiently high.
Usually, though, these are short pathways, and the model structure
one must work with, phamacokinetic (esp. physiologically-based PK)
models, do not have enough conservation relationships for the
approach of MCA to say much of anything. The relationship between
metabolism and circulatory levels of an active (pharmacology) or
toxic (toxicology) compound has been explored extensively in the
literature, and while there is still plenty of work to do--each
compound presents a new problem--it's probably not new or flashy
enough for Science. Combinatorial chem. is.
-Paul
