Preclinical herb-drug pharmacokinetic interaction of panax ginseng extract and selegiline in freely moving rats

Abstract

Selegiline, an inhibitor of monoamine oxidase B, is prescribed during the early stages of Parkinson's disease. The nutritional herbal medicine Panax ginseng C.A. Meyer has been reported to show potential neuroprotective activity; however, the herb-drug pharmacokinetic interaction between selegiline and P. ginseng extract has not been characterized. Our hypothesis is that the ginseng extract and selegiline produce pharmacokinetic interactions at certain doses. To investigate this hypothesis, a validated ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to monitor selegiline in rat plasma. Experimental rats were divided into groups treated with selegiline alone (10 mg/kg, i.v.; 30 mg/kg, p.o.), with the low-dose ginseng extract (1 g/kg, p.o., for 5 consecutive days) or with the high-dose ginseng extract (3 g/kg, p.o., for 5 consecutive days). The pharmacokinetic results demonstrated that the oral bioavailability of selegiline alone was approximately 18%; however, when rats were pretreated with low and high doses of the ginseng extract, the bioavailability of selegiline was 7.2 and 29%, respectively. These results suggested that the ginseng extract may produce a biphasic pharmacokinetic phenomenon. In summary, ginseng alters the oral bioavailability of selegiline, and these observations might provide preclinical information concerning the pharmacokinetic interactions between selegiline and herbal supplements.