English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Regorafenib, a multikinase inhibitor used in the treatment of various solid tumors, undergoes extensive uridine 5′‐diphosphate glucuronosyltransferase (Ugt)1a9‐mediated glucuronidation to form regorafenib‐N‐β‐glucuronide (M7;  RG ), but the contribution of hepatic uptake transporters, such as organic anion‐transporting polypeptide (Oatp)1b2, to the pharmacokinetics of regorafenib remains poorly understood. Using  NONMEM ‐based, population‐based, parent‐metabolite modeling, we found that Oatp1b2 and sex strongly impact the systemic exposure to  RG  in mice receiving oral regorafenib. Metabolic studies revealed that the liver microsomal expression of cytochrome P450 (Cyp)3a11 is twofold lower in female mice, whereas Ugt1a9 levels and function are not sex dependent. This finding is consistent with the metabolism of regorafenib occurring via two competing pathways, and the lack of Oatp1b2 results in decreased clearance of RG. The described model provides mechanistic insights into the  in vivo  disposition of regorafenib.

clinical and translational science

Interaction Between Sex and Organic Anion‐Transporting Polypeptide 1b2 on the Pharmacokinetics of Regorafenib and Its Metabolites Regorafenib‐N‐Oxide and Regorafenib‐Glucuronide in Mice