Pharmacology and pharmacokinetics studies of MBX-2982, a novel GPR119 agonists / 中国药学杂志

ABSTRACT

OBJECTIVE: To observe the glucose tolerance and evaluate the hypoglycemic effect of MBX-2982 respectively in the normal mice and in the KK-Ay mice. And further pharmacokinetics investigation was experimented in rats. METHODS: The influence of glucose tolerance was evaluated in KM mice which underwent a single dose of MBX-2982. Body weight, fasting blood glucose, glucose tolerance, triglyceride, serum insulin were all tested in order to evaluate the hypoglycemic effect on KK-Ay mice. The pharmacokinetics of MBX-2982 suspension and solution were investigated in rats to calculate the oral bioavailability. RESULTS: The blood glucose of each test point were all reduced after MBX-2982 (3, 10, 30 mg · kg-1) were administered orally to KM mice. After MBX-2982 (10, 30 mg · kg-1) treatment to KK-Ay mice for 4 weeks, the fasting blood glucose and triglyceride were significantly reduced and the serum insulin was remarkably increased. Meanwhile the area under glucose curve was significant reduced of 30 mg · kg-1. After oral administration of MBX-2982 (4 mg · kg-1) in rats, the oral bioavailability of suspension (0.4% CMC) and solution (DMSO-Cremopor EL-NS = 118) were 35.2% and 98.2% receptively. CONCLUSION: Animal experiment results show that the MBX-2982 as a GPR119 agonists had a good hypoglycemic effect. The absolute bioavailability of the solution is closed to 100%, which is higher than that of suspension.