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.


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.
Pfizer Oncology, San Diego, CA, USA.
Y
Y
Chen
J
J
Jiang
J
J
Zhang
M A
MA
Tortorici
Y K
YK
Pithavala
L
L
Lu
G
G
Ni
P
P
Hu
D000328:Adult; D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics*; D019540:Area Under Curve; D000077784:Axitinib; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics*; D007191:Indazoles / Q000493:pharmacokinetics*; D008297:Male
D020533:Angiogenesis Inhibitors; D007093:Imidazoles; D007191:Indazoles; D000077784:Axitinib