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KMID : 0369820080380050313
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Jorunal of Korean Pharmaceutical Sciences
2008 Volume.38 No. 5 p.313 ~ p.317
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Effects of Naringin on the Bioavailability of Etoposide in Rats
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Choi Byung-Chul
Choi Jun-Shik
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Abstract
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This study investigated the effect of naringin, a flavonoid, on the bioavailability of etoposide administered orally to rats. Etoposide (6 mg/kg) was administered orally to rats alone or with naringin (1, 4 or 12 mg/kg). Compared with the control group, the co-administration of etoposide with 4 and 12 mg/kg of naringin significantly (p<0.05) increased the area under the plasma concentration-time curve (AUC) and the peak plasma concentration (Cmax)of the oral etoposide. Consequently, the absolute bioavailability (AB) of etoposide in the presence (4 and 12 mg/kg) of naringin was significantly (p<0.05) increased by 9.4~10.6% compared with the control group (7.4%). The relative bioavailability (RB) of etoposide was increased 1.13- to 1.44-fold compared to the control group. Enhanced bioavailability of etoposide might be due to inhibition of both cytochrome P450 (CYP) 3A4 in the intestine or liver and P-glycoprotein (P-gp) transport efflux of etoposide in the intestinal membrane. This data indicate that careful consideration of the dosage for therapy with etoposide is required in a case of clinical application of the co-administration of etoposide and naringin.
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KEYWORD
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Etoposide, Naringin, Bioavailability, CYP3A4, P-gp, Rats
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