We hypothesize that a representation of drug-drug interactions (DDIs) based on physiologic, pharmacokinetic (PK) and pharmacodynamic (PD) mechanisms will provide more accurate and useful information to clinicians than current approaches that simply tabulate and index pairwise interactions of drugs. This paper explores the strengths, weaknesses, and difficulties of modeling drug mechanisms and reports on our initial work designing and implementing a drug KB based on qualitative pharmacokinetic mechanisms.