Population pharmacokinetic and exposure simulation analysis for cediranib (AZD2171) in pooled Phase I/II studies in patients with cancer.

ABSTRACT:

Aims

A population pharmacokinetic (PK) model was developed for cediranib to simulate cediranib exposure for different doses, including comedication with strong uridine glucuronosyl transferase/P-glycoprotein inducers such as rifampicin, in cancer patients.

Methods

Plasma concentrations and covariates from 625 cancer patients after single or multiple oral cediranib administrations ranging from 0.5 to 90 mg in 19 Phase I and II studies were included in the analysis. Stepwise covariate modelling was used to develop the population PK model. The final model was used to simulate cediranib exposure in cancer patients to evaluate cediranib target coverage and the need for dose adjustment for covariates or coadministration with rifampicin.

Results

A two-compartment model with

SUBMITTER: Li J 

PROVIDER: S-EPMC5510068 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature