Interaction of Cyclosporine A with Pomegranate Juice and Its Potential Nephroprotective Effect in Rats

Objectives: To study the effect of concomitant administering of pomegranate juice orally (PJ) on bioavailability of cyclosporine A (CsA) and independently its potential nephroprotective effect against CsA induced nephrotoxicity. Methods: A- Pharmacokinetic study (PK), Wister rats were divided into groups (each 6 rats) I-: CsA PO + Vehicle; II- CsA IP + Vehicle, III- CsA PO + PJ, IV- CsA IP + PJ. CsA dose was 20 mg/kg for 5 days the vehicle or PJ (2 ml) was given 1 h before drug administration. Blood samples were taken at the 1st and 5th day at specified times and CsA level was determined by immune assays. Relative bioavailability of CsA was determined. B-Nephroprotection study (separate study to administer bioequivalent CsA PO doses, in view of PK study), I- (CsA 13 mg PO + 2 ml PJ. II- CsA 20 mg P0 + 2 ml vehicle (for 28 day). The design also includes two control groups (vehicle alone or PJ alone). Blood samples for drug analysis, biochemical investigations and kidney samples for histopathology were taken at the 28th day. Results: PJ juice enhanced the bioavailability of oral CsA by about 50% (P > 0.05). But CsA (IP) was not affected after repeated administration for 5 days. Independently, the marked kidney damage induced by CsA was reversed by concomitant administration of PJ as well as it attenuated the increase in serum creatinine. Conclusions: Repeated administration of pomegranate juice enhance CsA oral bioavailability which likely due to inhibition of intestinal enzymes and transport pump. Independently it caused significant attenuation of CsA induced renal toxicity.