@entity43340 is one of the most important drug-metabolizing enzymes, determining the first-pass metabolism, oral bioavailability, and elimination of many drugs. It is also an important determinant of variable drug exposure and is involved in many drug-drug interactions. Recent studies with @entity43340 knockout and @entity19 have yielded a number of key insights that are important to consider during drug discovery and development. For instance, studies with tissue-specific @entity43340 - @entity19 have highlighted the importance of intestinal @entity43340 -dependent metabolism. They also revealed that intestinal @entity43340 plays an important role in the regulation of various @entity99 . Intestinal @entity43340 activity can thus have far-reaching pharmacological effects. Besides @entity43340 , the active drug efflux transporter P-glycoprotein also has a strong effect on the pharmacokinetics of numerous drugs. @entity43340 and P-glycoprotein have an extensive overlap in their substrate spectrum. It has been hypothesized that for many drugs, the combined activity of @entity43340 and P-glycoprotein makes for efficient intestinal first-pass metabolism of orally administered drugs as a result of a potentially synergistic collaboration. However, there is only limited in vitro and in vivo evidence for this hypothesis. There has also been some @entity911 in the field about what synergy actually means in this case. Our recent studies with @entity43340 /P-glycoprotein combination knockout @entity19 have provided further insights into the @entity43340 -P-glycoprotein interplay. We here present our view of the status of the synergy hypothesis and an attempt to clarify the existing @entity911 about synergy. We hope that this will facilitate further critical testing of the hypothesis and improve communication among researchers. Above all, the recent findings and insights into the interplay between @entity43340 and P-glycoprotein may have implications for improving oral drug bioavailability and reducing adverse side effects.

A critical analysis of the interplay between cytochrome P450 3A and P-glycoprotein: recent insights from knockout and XXXX .

@entity19 :: ('10090', 'Species') :: ['mice', 'transgenic mice'] @entity99 :: ('MESH:D056486', 'Disease') :: ['drug-handling systems in the liver'] @entity911 :: ('MESH:D003221', 'Disease') :: ['confusion'] @entity43340 :: ('13112(Tax:10090)', 'Gene') :: ['Cyp3a', 'CYP3A']
@entity19 :: (10090,Species) :: ['transgenic mice']
