Drug-drug interactions of P-gp substrates unrelated to CYP metabolism.

Drug-drug interactions of P-gp substrates unrelated to CYP metabolism. Curr Drug Metab. 2018 Oct 03;: Authors: Akamine Y, Yasui-Furukori N, Uno T Abstract In this decade, it is known that the role of several drug transporters is to act as a key player in drug disposition, and then they can affect clinical significances. Nevertheless, most of the drug-drug interaction (DDI) studies have been related to cytochrome P450s (CYPs), and these are followed by in vitro and in vivo drug-interactive reports on drug-transporters, which are accumulating. In addition, when both substrate drugs of CYPs and drug transporters (e.g., P-glycoprotein, P-gp) are related to DDIs, it remains that the mechanisms of DDIs will be quite ambiguous in assessing how much the CYPs and/or drug transporters partially contribute to DDIs. However, since fexofenadine is poorly metabolized by CYPs, the pharmacokinetics of fexofenadine transferring to the liver, kidney and blood-brain barrier primarily depend on the activities of multiple drug transporters. Accordingly, in the cases of fexofenadine DDI, it is unnecessary to consider that the CYPs effects are similar to those of DDIs of digoxin as a P-gp probed drug. Furthermore, unlike many cases of digoxin DDIs, it seems that fexofenadine primarily occurs in the gastrointestinal tract at the absorptional site but not in the kidney at the excretion site. Therefore, this article reviews the effects of potent P-gp inhibito...
Source: Current Drug Metabolism - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Metab Source Type: research