Pharmacokinetics of the Monocarboxylate Transporter 1 Inhibitor AZD3965 in Mice: Potential Enterohepatic Circulation and Target-Mediated Disposition.

ABSTRACT:

Purpose

To evaluate the pharmacokinetics (PK) of the monocarboxylate transporter 1 (MCT1) inhibitor AZD3965 in mice after IV and oral administration and to develop mechanistic PK models to assess the potential enterohepatic circulation (EHC) and target-mediated drug disposition (TMDD) of AZD3965.

Methods

Female BALB/c mice were administered AZD3965 by IV injection (10, 50 and 100 mg/kg) or oral gavage (100 mg/kg). Plasma samples were analyzed using LC/MS/MS, and PK parameters determined by compartmental and non-compartmental analyses.

Results

AZD3965 exhibited a large volume of distribution and rapid oral absorption, with a high oral bioavailability. Prominent reentry peaks were observed after both oral and IV administration, suggesting potential EHC of AZD3965 or of

SUBMITTER: Guan X 

PROVIDER: S-EPMC8164216 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature