Effect of mushroom diet on pharmacokinetics of gabapentin in healthy Chinese subjects

摘要

AimsThis study evaluated the pharmacokinetics of gabapentin in Chinese subjects who received a diet rich in shiitake mushrooms. Shiitake mushrooms have been shown to contain high amount of ergothioneine. In vitro studies have shown that OCTN1-mediated secretion of gabapentin is trans-stimulated by ergothioneine. This study also investigated the concentrations of ergothioneine in plasma at baseline and following mushroom consumption.MethodsTen healthy male subjects were recruited and received a diet containing no mushrooms (treatment A) or a high mushroom diet (treatment B; after at least a 7 day washout period) 1 day prior to administration of a single oral dose of gabapentin 600?mg.ResultsIngestion of shiitake mushrooms produced significant increases in plasma ergothioneine concentrations that were sustained for more than 48?h. A statistically significant but modest increase in the renal clearance (CL_R) of gabapentin occurred after intake of the mushroom diet (91.1?±?25.1 vs. 76.9?±?20.6?ml?min?1, P?=?0.031). No significant changes in AUC(0,t_last) of gabapentin were observed (P?=?0.726). Creatinine clearance did not correlate with CL_R of gabapentin at baseline (treatment A). After ingestion of the mushroom diet, creatinine clearance accounted for 65.3% of the variance in CL_R of gabapentin.ConclusionsThese data suggest that diet–drug pharmacokinetic interactions may occur during co-exposure to gabapentin and mushroom constituents. However, as it does not affect the AUC(0,t_last) of gabapentin, it may not have clinically important consequences. Shiitake mushrooms can also be used as a source of ergothioneine for future clinical studies.