Alterations in cytochrome P4503A4 are the most frequent underlying cause of drug-drug interactions (DDIs). This enzyme exhibits some unusual behaviors; for example, it has been observed that certain inhibitors can affect some CYP3A4-catalyzed reactions more than others, even for the same substrate. This has been proposed to be due to the simultaneous binding of more than one ligand to the enzyme. This behavior has been frequently observed in vitro, but seldom are analogous effects evident in vivo.