A Phase I study to evaluate the pharmacokinetics of axitinib (AG-13736) in healthy Chinese volunteers.

OBJECTIVE

To assess axitinib plasma pharmacokinetics and safety of single oral doses of axitinib under fed conditions in healthy Chinese volunteers.

MATERIALS AND METHODS

This Phase I, open-label study evaluated single dosing of axitinib in 14 healthy Chinese volunteers. Axitinib was administered as 5-, 7-, and 10-mg doses under fed conditions in study periods 1, 2, and 3, respectively, followed by pharmacokinetic assessments and safety monitoring. A washout period ≥ 7 days was provided between successive axitinib doses. Blood samples were collected during each period up to 32 h post-dose for pharmacokinetic analysis. Axitinib plasma pharmacokinetic parameters were estimated using standard noncompartmental methods.

RESULTS

Estimates (geometric mean) of axitinib AUC(inf) were 150, 251, and 321 ng × h/ml for doses of 5, 7, and 10 mg, respectively, reflecting a dose-proportional increase in AUC(inf) (increments of 1 : 1.7 : 2.1 for dose increments of 1 : 1.4 : 2, respectively). Geometric mean estimates of maximum observed plasma concentration (Cmax) were 33.5, 51.1, and 69.4 ng/ml, respectively, which also showed dose proportionality. Axitinib plasma pharmacokinetics was similar to those previously observed in healthy Caucasians, with geometric mean values (% geometric coefficient of variation) for axitinib plasma AUC(inf) 150 ng × h/ml (62%) versus 125 ng × h/ml (60%), respectively. Axitinib was well tolerated, with no serious adverse events or discontinuations; one adverse event of mild abdominal distension was observed.

CONCLUSIONS

In healthy Chinese subjects, single dosing of axitinib demonstrated dose-proportional pharmacokinetics. Axitinib pharmacokinetics in this population was similar to those previously observed in healthy Caucasians, suggesting a lack of ethnic differences.