title: Axitinib plasma pharmacokinetics and ethnic differences.
abstract: Axitinib, a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, showed improved progression-free survival over sorafenib in patients previously treated for advanced renal cell carcinoma in the AXIS trial. Although a few studies had established the efficacy and safety of axitinib in Asian patients, additional evaluation was necessary to obtain regulatory approval in several Asian countries, especially in light of ethnic differences that are known to exist in genetic polymorphisms for metabolizing enzymes such as cytochrome P450 (CYP) 3A5, CYP2C19 and uridine diphosphate glucuronosyltransferase (UGT) 1A1, which are involved in axitinib metabolism. Axitinib plasma pharmacokinetics following single or multiple administration of oral axitinib in Asian (Japanese or Chinese) healthy subjects as well as Asian patients with advanced solid tumors was compared with that obtained in Caucasians. Upon review, the data demonstrated that axitinib can be characterized as not sensitive to ethnic factors based on its pharmacokinetic and pharmacodynamic properties. Axitinib exhibited similar pharmacokinetics in Asian and non-Asian subjects. A pooled population pharmacokinetic analysis indicated lack of a clinically meaningful effect of ethnicity on axitinib disposition. Therefore, dose adjustment for axitinib on the basis of ethnicity is not currently warranted.
authors: Clinical Pharmacology, Pfizer Inc, 10555 Science Center Drive, San Diego, CA, 92121, USA.
authors: Ying
authors: Y
authors: Chen
authors: Akiyuki
authors: A
authors: Suzuki
authors: Michael A
authors: MA
authors: Tortorici
authors: May
authors: M
authors: Garrett
authors: Robert R
authors: RR
authors: LaBadie
authors: Yoshiko
authors: Y
authors: Umeyama
authors: Yazdi K
authors: YK
authors: Pithavala
mesh_terms: D019540:Area Under Curve; D044466:Asian People; D000077784:Axitinib; D002681:China; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D006207:Half-Life; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007191:Indazoles / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007564:Japan; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors*; D044465:White People
chemical_list: D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D042442:Vascular Endothelial Growth Factors; D000077784:Axitinib