Effects of coadministrations of unripe fruits and ripe peels of citrus aurantium on cyclosporine pharmacokinetics in rats

The unripe fruits (UF) and ripe peels (RP) of Citrus aurantium are two widely used Chinese herbs. Cyclosporine, an important immunosuppressant with narrow therapeutic window, is clinically subject to relevant interaction with Citrus herbs as with grapefruit juice. This study investigated the effects of coadministration of UF and RP on cyclosporine pharmacokinetics in rats. Sprague-Dawley rats received cyclosporine (2.5 mg/kg) orally with and without the UF and RP decoctions individually. Blood samples taken via cardiopuncture were assayed for cyclosporine by a specific monoclonal fluorescence polarization immunoassay. After coadministration orally with UF decoction, the C_max and AUC_0-t of cyclosporine were significantly decreased by 72.8% and 55.6%, respectively. However, when RP was coadministered orally, no conspicuous alteration of cyclosporine pharmacokinetics was observed. It can be concluded that UF, but not RP decoction, significantly decreased the bioavailability of oral cyclosporine. We suggest that coadministration of Citrus herbs with cyclosporine is better avoided to ensure the efficacy and safety of cyclosporin medication.