[Predicting pharmacokinetics of anti-cancer drug, famitinib in human using physiologically based pharmacokinetic model].
This study is to establish physiologically based pharmacokinetic (PBPK) models of famitinib in rat and monkey, and then to predict the pharmacokinetics and tissue distribution of famitinib in human based on the PBPK models. According to published paper, previous studies and the chemical properties of famitinib predicted by ACD/ADME suite and SimCYP, the PBPK models of rat and monkey were established and optimized using GastroPlus. And then, the PBPK models were applied to predict the pharmacokinetic and tissue distribution of famitinib in human. The results showed that the PBPK models of rat and monkey can fit the observed data well, and the AUC0-∞, ratios of observed and calculated data in rat and monkey were 1.00 and 0.97, respectively. The AUC0-∞, ratios of observed and predicted data in human were 1.63 (rat to human) and 1.57 (monkey to human), respectively. The rat and monkey PBPK models of famitinib were well established, and the PBPK models were applied in predicting pharmacokinetic of famitinib in human successfully. Hence, the PBPK model of famitinib in human could be applied in future drug-drug interaction study.
Ming-Ming
MM
Yu
Zhi-Wei
ZW
Gao
Xiao-Yan
XY
Chen
Da-Fang
DF
Zhong
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D000882:Haplorhini; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics*; D008954:Models, Biological; D011758:Pyrroles / Q000493:pharmacokinetics*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; C584390:famitinib; D020794:Receptor Protein-Tyrosine Kinases