Population pharmacokinetic and exposure simulation analysis for cediranib (AZD2171) in pooled Phase I/II studies in patients with cancer
| Autor: | Eric Masson, Jianguo Li, Weifeng Tang, Anja Henningsson, Nidal Al-Huniti |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pharmacology education.field_of_study business.industry Population Cancer medicine.disease Pharmacometrics Vascular endothelial growth factor Cediranib 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine chemistry Pharmacokinetics 030220 oncology & carcinogenesis medicine Pharmacology (medical) business education IC50 Rifampicin medicine.drug |
| Zdroj: | British Journal of Clinical Pharmacology. 83:1723-1733 |
| ISSN: | 0306-5251 |
| DOI: | 10.1111/bcp.13266 |
| Popis: | 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 sequential zero- and first-order absorption and first-order elimination adequately described the cediranib concentration–time courses. Body weight and age were identified as having statistically significant impact on cediranib PK, but only |
| Databáze: | OpenAIRE |
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