In vitro and physiologically-based pharmacokinetic based assessment of drug-drug interaction potential of canagliflozin.

ABSTRACT:

Aims

Canagliflozin is a recently approved drug for use in the treatment of type 2 diabetes. The potential for canagliflozin to cause clinical drug-drug interactions (DDIs) was assessed.

Methods

DDI potential of canagliflozin was investigated using in vitro test systems containing drug metabolizing enzymes or transporters. Basic predictive approaches were applied to determine potential interactions in vivo. A physiologically-based pharmacokinetic (PBPK) model was developed and clinical DDI simulations were performed to determine the likelihood of cytochrome P450 (CYP) inhibition by canagliflozin.

Results

Canagliflozin was primarily metabolized by uridine 5'-diphospho-glucuronosyltransferase 1A9 and 2B4 enzymes. Canagliflozin was a substrate of efflux transporters (P-gl

SUBMITTER: Mamidi RNVS 

PROVIDER: S-EPMC5401984 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature