Pharmacokinetic interaction between pazopanib and cisplatin regimen

Cancer Chemotherapy and Pharmacology
Diane-Charlotte ImbsE Chatelut

Abstract

A phase I study combining daily oral pazopanib and cisplatin (given iv every 3 weeks) was performed in order to determine the maximum tolerated dose of both drugs in combination. Pharmacokinetic interactions were evaluated. Plasma pazopanib and ultrafilterable cisplatin concentrations were obtained in 32 patients treated according to four levels of dose corresponding to 200, 400 or 600 mg daily dose of pazopanib and 60 or 75 mg/m(2) of cisplatin. Two sequences of treatment were performed in order to explore any interaction of cisplatin on pazopanib pharmacokinetics and inversely. Data were analyzed using the NONMEM program. Maximum tolerated dose was 400 mg of pazopanib and 75 mg/m(2) of cisplatin. Mean (CV % for inter-individual variability) cisplatin clearance was 10.3 L/h (33.2 %) and appeared not to be influenced by pazopanib. However, pazopanib pharmacokinetics was significantly modified by the cisplatin regimen. Mean (CV %) of oral pazopanib clearance was 0.66 L/h (55 %) at Day 0 (before cisplatin administration), 24.8 % lower at Day 1 and 32.9 % lower at Day 2. The interaction is less likely to be due to cisplatin than to a competitive inhibition of pazopanib metabolism and efflux by aprepitant, an antiemetic drug system...Continue Reading

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Citations

May 15, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·C SauzayF Thomas
Aug 25, 2016·Expert Opinion on Drug Metabolism & Toxicology·Pascaline Boudou-RouquetteFrançois Goldwasser
May 5, 2017·British Journal of Clinical Pharmacology·Priya PatelL Lee Dupuis
Jul 6, 2017·Expert Opinion on Drug Metabolism & Toxicology·Simone FerreroDomenica Lorusso
Oct 28, 2018·Clinical Pharmacokinetics·Sander BinsStijn L W Koolen
Oct 28, 2019·Clinical Pharmacokinetics·Belén P SolansIñaki F Trocóniz
Feb 12, 2017·Clinical Pharmacokinetics·Remy B VerheijenNeeltje Steeghs
Mar 16, 2021·Journal of Geriatric Oncology·Loïc MoureyEtienne Chatelut

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