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

被引:11
作者
Toh, Dorothy Su Lin [1 ,2 ]
Limenta, Lie Michael George [2 ]
Yee, Jie Yin [2 ]
Wang, Ling-Zhi [2 ,3 ]
Goh, Boon-Cher [2 ,3 ,4 ]
Murray, Michael [5 ]
Lee, Edmund Jon Deoon [2 ]
机构
[1] Univ Sydney, Fac Pharm, Sydney, NSW 2006, Australia
[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore 117597, Singapore
[3] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117597, Singapore
[4] Natl Univ Hlth Syst, Dept Hematol & Oncol, Singapore, Singapore
[5] Univ Sydney, Discipline Pharmacol, Sydney, NSW 2006, Australia
关键词
ergothioneine; gabapentin; mushroom; novel human organic cation transporter 1; pharmacokinetics; LIQUID-CHROMATOGRAPHY; HUMAN PLASMA; CULTIVATED MUSHROOMS; ERGOTHIONEINE; QUANTIFICATION; TRANSPORTER; OCTN1;
D O I
10.1111/bcp.12273
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Aims This 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. Methods Ten 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 600mg. Results Ingestion of shiitake mushrooms produced significant increases in plasma ergothioneine concentrations that were sustained for more than 48h. A statistically significant but modest increase in the renal clearance (CLR) of gabapentin occurred after intake of the mushroom diet (91.1 +/- 25.1 vs. 76.9 +/- 20.6mlmin-1, P=0.031). No significant changes in AUC(0,tlast) of gabapentin were observed (P=0.726). Creatinine clearance did not correlate with CLR of gabapentin at baseline (treatment A). After ingestion of the mushroom diet, creatinine clearance accounted for 65.3% of the variance in CLR of gabapentin. Conclusions These 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,tlast) of gabapentin, it may not have clinically important consequences. Shiitake mushrooms can also be used as a source of ergothioneine for future clinical studies.
引用
收藏
页码:129 / 134
页数:6
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