Country: Бангладеш
Језик: Енглески
Извор: DGDA (Directorate General of Drug Administration)
Axitinib
Beacon Pharmaceuticals PLC
Axitinib
1 mg
Tablet
COMPOSITION Axinix 1 Tablet: Each film coated tablet contains Axitinib INN 1 mg. Axinix 5 Tablet: Each film coated tablet contains Axitinib INN 5 mg. CLINICAL PHARMACOLOGY Mechanism of Action Axitinib has been shown to inhibit receptor tyrosine kinases including vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression. VEGF-mediated endothelial cell proliferation and survival were inhibited by Axitinib in vitro and in mouse models. Axitinib was shown to inhibit tumor growth and phosphorylation of VEGFR-2 in tumor xenograft mouse models. Pharmacodynamics The effect of a single oral dose of Axitinib (5 mg) in the absence and presence of 400 mg Ketoconazole on the QTc interval was evaluated in a Randomized, single-blinded, two-way crossover study in 35 healthy subjects. No large changes in mean QTc interval (i.e., >20 ms) from placebo were detected up to 3 hours post-dose. However, small increases in mean QTc interval (i.e., <10 ms) cannot be ruled out. Pharmacokinetics The population pharmacokinetic analysis pooled data from 17 trials in healthy subjects and patients with cancer. A two-compartment disposition model with first-order absorption and lag-time adequately describes the Axitinib concentration-time profile. Absorption and Distribution: Following single oral 5-mg dose administration, the median T max ranged from 2.5 to 4.1 hours. Based on the plasma half-life, steady state is expected within 2 to 3 days of dosing. Dosing of Axitinib at 5 mg twice daily resulted in approximately 1.4-fold accumulation compared to administration of a single dose. At steady state, Axitinib exhibits approximately linear pharmacokinetics within the 1-mg to 20-mg dose range. The mean absolute bioavailability of Axitinib after an oral 5 mg dose is 58%. Compared to overnight fasting, administration of Axitinib with a moderate fat meal resulted in 10% lower AUC and a high fat, high- Прочитајте комплетан документ