Pharmacokinetics and Bioavailability of Norisoboldine and its Metabolite in Rats

OBJECTIVE To investigate the in vivo pharmacokinetic properties and bioavailability of norisoboldine and its major metabolite in rats after intravenous and oral administration. METHODS A UPLC-MS method was used to determine the plasma concentrations of norisoboldine and norisoboldine-9-O-α-glucuronide in rats plasma. The pharmacokinetic parameters were calculated with PK solution software. RESULTS The absolute bioavailabilities for norisoboldine and norisoboldine-9-O-α-glucuronide were 2.77% and 88.6%, respectively. After intravenous injection of norisoboldine, the main pharmacokinetic parameters of norisoboldine and norisoboldine-9-O-α-glucuronide were as follows: t_1/2 (42.16±36.56) and (275.26±176.89) min, AUC_0-t(55.25±22.97) and (584.57±216.18)mg·min·mL^-1, k_e (0.024 9±0.012 9) and (0.003 7±0.002 4)min^-1, respectively. Their major pharmacokinetic parameters after oral administration were as follows: C_max (0.14±0.03) and (13.80±1.46)mg·mL^-1, T_max (3.33±13.29) and (45.00±9.49)min, t_1/2 (30.20±11.04) and (313.79±181.20)min, AUC_0-t (9.17±2.44) and (3 108.69±299.45) mg·min·mL^-1, k_e (0.025 2±0.007 6) and (0.002 7±0.001 0)min^-1, respectively. There were significant differences between oral and intravenous administration in t_1/2, AUC_0-t, T_max, C_max, k_e and MRT (P<0.05). CONCLUSION The absolute bioavailability for norisoboldine was poor in rats. Norisoboldine could be quickly biotransformed into norisoboldine-9-O-α-glucuronide, a major metabolite of parent drug in vivo, and the plasma concentration of norisoboldine-9-O-α-glucuronide was considerably higher than that of the parent drug.