A semi-mechanistic absorption model to evaluate drug-drug interaction with dabigatran: application with clarithromycin.

ABSTRACT:

Aim

The aim of this study was to develop a PK/PD model to assess drug-drug interactions between dabigatran and P-gp modulators, using the example of clarithromycin, a strong inhibitor of P-gp.

Methods

Ten healthy male volunteers were randomized to receive in the first treatment period a single 300 mg dose of dabigatran etexilate (DE) and in the second treatment period 500 mg clarithromycin twice daily during 3 days and then 300 mg DE plus 500 mg clarithromycin on the fourth day, or the same treatments in the reverse sequence. Dabigatran plasma concentration and ecarin clotting time (ECT) were measured on 11 blood samples. Models were built using a non-linear mixed effect modelling approach.

Results

The best PK model was based on an inverse Gaussian absorption process

SUBMITTER: Delavenne X 

PROVIDER: S-EPMC3703233 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature