Naringin and Naringenin Pharmacokinetics and the Influence of Naringenin on Cyclosporin Absorption

• Main Authors: TANG-YEN HUANG, 黃堂彥
• Other Authors: Pei-Dawn Lee Chao
• Format: Others
• Language: zh-TW
• Published: 1999
• Online Access: http://ndltd.ncl.edu.tw/handle/86518252626237216403

碩士 === 中國醫藥學院 === 藥物化學研究所 === 87 === Naringin and naringenin are bioactive natrual products. The pharmacokinetics of naringin and naringenin were investigated in New Zealand white rabbits. The serum concentrations of metabolites of naringin and naringenin were assayed by HPLC method after incubation at 37 ℃ for 4 hours with β-glucuronidase/sulfatase. The analysis was carried out on a RP-18 column, using acetonitrile-1 % acetic acid (36:64, v/v) as mobile phase at a flow rate of 1 ml/min. The detection was set at 287 nm and 5,7-dimethoxycoumarin was used as the internal standard. The precision and accuracy of this method and the recoveries were satisfactory. The limit of quantitation (LOQ) was 50.00 ng/ml, the limit of detection (LOD) was 6.25 ng/ml. After iv bolus of naringenin, the serum concentration of naringenin declined rapidly with an elimination half life of 17 min. The Vd was 1.6 L, the AUC was 1693.2 nmol.min/ml, and the CL was 0.16 L/min. The absorption of naringenin after oral administration was 8 %. The much higher percentage of conjugates after oral route than iv bolus indicated the significant first pass metabolism of naringenin at gut wall and liver. After oral administration of naringin, the absorption showed comparable extent with that of naringenin. The effect of sugars on the absorption of naringin indicated that honey, sucrose and fructose, but not glucose, significantly decreased the absorption of naringin. Cyclosporin is a potent immunosuppressive agent with narrow therapeutic range. The mean systematic bioavailability is about 30 %. CYP3A4 and P-glycoprotein are involved in the first pass extraction of cyclosporin. Blood cyclosporin concentrations were determined by FPIA method. After oral coadministration of cyclosporin with naringenin, the AUC0-t and Cmax of cyclosporin were increased 83.7 % (p= 0.010) and 75.0 % (p= 0.027), respectively, in four rats, and decreased 56.7 % (p= 0.028) and 65.9 % (p= 0.046) , respectively, in six rats, indicating naringenin was an inducer of P-glycoprotein. The influence of naringenin on cyclosporin absorption was variable among individuals. Therefore, when naringenin was codministered with cyclosporin, the blood cyclosporin concentration should be carefully monitored.