关键词: pazopanib, 细胞色素P450 3A4, 基因多态性

Abstract: AIM: To study the pharmacokinetics (PK) of pazopanib tablets and explore the genetic mechanism of individual differences in drug metabolism primarily.  METHODS: Fourteen healthy male subjects were respectively administrated with a single dose pazopanib tablet (200 mg) orally on the day of dosing, and their blood samples were collected from baseline to 96 hours. The serum concentration of pazopanib was measured by LC-MS/MS, the parameters of PK were calculated by winnonlin 6.3 software, and the gene polymorphism of cytochrome P450 3A4 (CYP3A4) was determined by snapshot method. RESULTS: The range of Cmax was (7 361.65-26 081.00) ng/mL, with an average±sd of (15 410.72±6 366.21) ng/mL; the range of tmax was (1.50-4.00) h, with an average±sd of (2.50±0.83) h; AUC0-t range was (228 013.55-775 231.63) ng·mL-1·h, average±sd was (516 279.90±175 688.41) ng·mL-1·h; tmax could differ by more than 2 times between individuals, and Cmax and AUC could differ by more than 3 times. CYP3A4 site (rs35599367) of 14 subjects were all wild-type. CONCLUSION: The pazopanib tablets have large individual differences among Chinese healthy male volunteers, but no CYP3A4 (rs35599367) polymorphism differences were observed in this study. Individual PK differences of pazopanib may be related to polymorphisms of other drug metabolism related genes.

Key words: pazopanib, cytochrome P450 3A4, gene polymorphism