Food-drug interaction of tacrolimus with pomelo, ginger, and turmeric juice in rats.
ABSTRACT Tacrolimus is a well-known potent immunosuppressant agent, which has various drug-drug or food-drug interactions. Previously, we found a renal transplant recipient who increased tacrolimus blood concentrations after ingestion of pomelo as a rare case. So, we investigated the effect of pomelo after its administration for one day or 3 consecutive days on the pharmacokinetics of tacrolimus in rats. We also confirmed the effects of grapefruit, turmeric, and ginger. The tacrolimus blood concentrations of the rats pre-treated with 100% pomelo juice were significantly higher than those pre-treated with water. On the other hand, the tacrolimus blood concentrations of the rats pre-treated with 50% pomelo juice were not significantly different from those pre-treated with water. The pomelo-tacrolimus interaction showed concentration dependency. Even low concentration of pomelo juice could enhance the blood concentrations of tacrolimus by repeated administration. The inhibitory effect of 100% pomelo juice disappeared 3 days after intake. The AUC values of tacrolimus in the rats pre-treated with grapefruit juice, ginger juice, and turmeric juice were significantly larger than those pre-treated with water. We could confirm the pomelo-tacrolimus interaction, which we discovered in a case study, quantitatively. We newly found the influence of turmeric and ginger on tacrolimus pharmacokinetics, comparable to pomelo.
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ABSTRACT: Ginger has been extensively used as a herbal medicine for thousands of years in Asia; it has also been used as a seasoning agent in several foods and beverages worldwide. In this study, the effect of an aqueous-ethanolic extract of ginger on CYP450-mediated drug metabolism was investigated in vitro to elucidate the herb-drug interactions. A CYP450-specific substrates mixture was incubated with an aqueous-ethanolic extract of ginger in human liver microsomes fortified with an NADPH-generating system, and the metabolites generated from each of the CYP450-specific metabolic reactions were measured by liquid chromatography-tandem mass spectrometry. The ginger extracts were tested at concentrations of 0.05-5 microg/mL. The resulting data showed that the ginger extract inhibited CYP2C19-mediated drug metabolism in a concentration-dependent manner with an IC50 value of 3.8 microg/mL. When the ginger extract was pre-incubated and assessed, the inhibition pattern did not change, indicating that the inhibition of CYP2C19 was competitive rather than mechanism-based. The effects on other CYP isozyme activity were negligible at the concentrations tested. In conclusion, this inhibitory effect of ginger extract could affect the pharmacokinetics and lead to interactions with drugs that are metabolized by CYP2C19.Pharmazie 12/2012; 67(12):1007-9. DOI:10.1691/ph.2012.2595 · 1.00 Impact Factor