CONCLUSIONS AND FUTURE DIRECTIONS It is difficult to assess the true incidence and clinical significance of drug interac- tions Understanding the mechanisms underlying drug interactions is important for the prediction and avoidance of drug toxicity when initiating combination therapy. Although multiple in vitro methods are currently in use to assess drug interactions, not all have allowed the prediction of clinically significant events (202,203) . As drug interactions most commonly result from influences on drug-metabolizing enzymes, future research defining the origins of enzyme activity variability and characterizing individual patient activity will certainly improve our ability to predict these interac- tions and improve drug therapy.