A Phase I Study of the Pharmacokinetic and Safety Profiles of Oral Pazopanib With a High-Fat or Low-Fat Meal in Patients With Advanced Solid Tumors

作者：Heath E I^*; Chiorean E G; Sweeney C J; Hodge J P; Lager J J; Forman K; Malburg L; Arumugham T; Dar M M; Suttle A B; Gainer S D; LoRusso P

来源：Clinical Pharmacology & Therapeutics, 2010, 88(6): 818-823.

DOI：10.1038/clpt.2010.199

Pazopanib is an oral angiogenesis inhibitor of vascular endothelial growth factor (VEGF) receptor, platelet-derived growth factor receptor, and cytokine receptor. This open-label, randomized, crossover, phase I study evaluated the effect of low- and high-fat meals on the pharmacokinetics (PK) of pazopanib in patients with advanced solid tumors. Patients participated in either the lead-in cohort or randomized food-effect cohort. Patients in the lead-in cohort were administered a single dose of pazopanib 400 mg with a high-fat meal. Patients in the food-effect cohort were randomized to receive single doses of pazopanib 800 mg in fed condition (high- or low-fat meal) or fasting condition, in random sequence 14 days apart. After completion of the study, patients were given the opportunity to continue treatment with daily pazopanib 800 mg. Administration of pazopanib with both low- and high-fat meals increased maximum observed plasma concentration (C(max)) and area under the plasma concentration time curve (AUC) by approximately twofold as compared with the corresponding values when administered to patients in the fasted condition. Therefore, pazopanib should be administered to patients in the fasted state so as to minimize within- and between-day variability in the systemic exposure to pazopanib in patients with cancer.

• 出版日期2010-12