Pharmacokinetics and tissue distribution of ipriflavone, an isoflavone derivative, after intravenous administration to rabbits

Pharmacokinetic parameters of ipriflavone and its main metabolites, M1 and M5, after intravenous administration of spray-dried ipriflavone, SIP (10, 20, and 30 mg/kg as ipriflavone) and tissue distribution of ipriflavone, M1, and M5 after intravenous administration of SIP (20 mg/kg as ipriflavone) were evaluated in rabbits. Saturable metabolism of ipriflavone were observed after intravenous administration; at an ipriflavone dose of 30 mg/kg, the dose-normalized (based on 10 mg/kg) AUC was significantly greater (72.4 and 64.0 versus 103 mug min/mL), Cl was significantly slower (138 and 156 versus 97.6 mL/min/kg), and terminal half-life (94.8 and 129 versus 211 min) and mean residence time (91.3 and 116 versus 186 min) were significantly longer than those at 10 and 20 mg/kg. The AUC of M1 was also significantly greater at ipriflavone dose of 30 mg/kg. The terminal half-life, AUG, and renal clearance of M5 were also significantly different at ipriflavone dose of 30 mg/kg than those at 10 and 20 mg/kg. Ipriflavone was widely distributed in most rabbit tissues studied and the tissue-to-plasma (T/P) ratios of ipriflavone were greater than unity in all tissues (or organs) studied except spleen, indicating that ipriflavone has high affinity to rabbit tissues studied, and this could be supported by considerably high values of the apparent volume of distribution of ipriflavone at steady state (11400-16900 mL/kg). M1 and M5 were also detected in most rabbit tissues with considerable amount of M1 (T/P ratio of 9.43) and M5 (T/P ratio of 4.66) in the kidney. Copyright (C) 2000 John Wiley & Sons, Ltd.