title: Effect of mushroom diet on pharmacokinetics of gabapentin in healthy Chinese subjects.
abstract: OBJECTIVE
  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 600 mg.
  
  
  RESULTS
  Ingestion 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 (CLR ) 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,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.
authors.affiliation: Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Dorothy Su Lin
authors.initials: DS
authors.lastname: Toh
authors.forename: Lie Michael George
authors.initials: LM
authors.lastname: Limenta
authors.forename: Jie Yin
authors.initials: JY
authors.lastname: Yee
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Wang
authors.forename: Boon-Cher
authors.initials: BC
authors.lastname: Goh
authors.forename: Michael
authors.initials: M
authors.lastname: Murray
authors.forename: Edmund Jon Deoon
authors.initials: EJ
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000363:Agaricales / Q000737:chemistry; D000588:Amines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics; D044466:Asian People / Q000235:genetics; D002681:China; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004032:Diet; D004880:Ergothioneine / Q000097:blood*; D000077206:Gabapentin; D005838:Genotype; D064368:Healthy Volunteers; D041743:Herb-Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D027701:Organic Cation Transport Proteins / Q000235:genetics; D027981:Symporters; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; D027981:Symporters; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D004880:Ergothioneine
keywords: ergothioneine; gabapentin; mushroom; novel human organic cation transporter 1; pharmacokinetics