| In Vivo |
ONO-8430506 (10 mg/kg/day; gavage; for 21 days) slows initial tumor growth and limits lung metastasis[1]. ONO-8430506 decreases the initial phase of breast tumor growth and subsequent lung metastases by ~60% in a syngeneic orthotopic mouse model[1]. ONO-8430506 (oral; 30 mg/kg) demonstrates good pharmacokinetics and persistently inhibits plasma lysophosphatidic acid formation in rats[2]. ONO-8430506 (30 or 100 mg/kg) enhances the antitumor effect of Paclitaxel in a breast cancer model[3]. ONO-8430506 exhibits moderate oral bioavailability (rat 51.6%, dog 71.1%, and monkey 30.8%) and Cmax (rat 261, dog 1670, and monkey 63 ng/mL) following oral administration (rat 1, dog 1, and monkey 1 mg/kg)[3]. ONO-8430506 exhibits terminal elimination half-lives (rat 3.4, dog 8.9, and monkey 7.9 h) due to low plasma clearance (8.2, 4.7, and 5.8 mL/min/kg respectively) combined with large volumes of distribution (1474, 1863, and 2275 mL/kg respectively) following intravenous administration (rat 0.3, dog 0.3, and monkey 0.3 mg/kg)[3]. Animal Model: Female BALB/c mice, 8-10 wk old (BALB/cAnNCrl)[1] Dosage: 10 mg/kg Administration: Gavaged daily for 21 days; 10 μL/g Result: Tumor growth in ONO-8430506-treated mice caught up to the vehicle group by day 13; thereafter, primary tumor size was not significantly different from the vehicle-treated mice. However, treatment with ONO-8430506 decreased the numbers of metastatic nodules in the lungs at day 21 by ~60%.
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