It is well established that ethanol is an inhibitor of cocaine metabolism, a drug that is eliminated by carboxylesterase hydrolysis. We propose that the ethanol-mediated inhibition of carboxylesterases activity demonstrated with cocaine metabolism will occur with other substrate drugs. This has widespread implications because of the large number of drugs that are carboxylesterase substrates. In the United States, over 100 million people consume ethanol making co-ingestion with carboxylesterase substrate drugs a common occurrence. We believe that this is a prevalent drug interaction that is largely overlooked and has not been systematically evaluated, but may importantly affect the disposition, safety, and efficacy of these medications. To address this gap, we will evaluate the effect of ethanol on the disposition of oseltamivir, an hCE1 substrate, and aspirin, an hCE2 substrate, in humans.