Ponatinib (Iclusig)
(Ariad) Absolute bioavailability unknown; peak concentrations within 6 h of dosing; following 45 mg dose: Cmax = 73 ng/mL; AUC = 1253 ng•hr/mL;
Vd= 1223 L (oral administration, 45 mg ponatinib once daily for 28 days);
(weak substrate for P-gp and ABCG2) Metabolized by CYP3A4 and to a lesser extent CYP2C8, CYP2D6, CYP3A5 involved in phase I metabolism in vitro; esterases and/or amidases Commence treatment at 45 mg once daily (chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia) (due to severe vascular occlusive events at this dose lower doses are being explored);
start at 30 mg once daily (patients taking strong CYP3A inhibitors; patients with hepatic impairment);
>99 % binding Pulmonary arterial hypertension has been reported for ponatinib (206)