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Brain Extracellular γ-hydroxybutyrate Concentrations are Decreased by L-lactate in Rats: Role in the Treatment of Overdoses.
MedLine Citation:
PMID:  23319173     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: L-lactate represents a potential treatment for GHB overdose by inhibiting GHB renal reabsorption mediated by monocarboxylate transporters. Our objective was to assess the dose-dependence of L-lactate treatment, with and without D-mannitol, on GHB toxicokinetics/toxicodynamics (TK/TD). METHODS: Rats were administered GHB 600 mg/kg i.v. with L-lactate (low and high doses), D-mannitol, or L-lactate (low dose) with D-mannitol. GHB-induced sleep time and GHB plasma, urine and brain extracellular fluid (ECF) concentrations (by LC/MS/MS) were determined. The effect of L-lactate and D-mannitol on the uptake and efflux of GHB was assessed in rat brain endothelial RBE4 cells. RESULTS: L-lactate treatment increased GHB renal clearance from 1.4 ± 0.1 ml/min/kg (control) to 2.4 ± 0.2 and 4.7 ± 0.5 ml/min/kg after low and high doses, respectively, and reduced brain ECF AUC values to 65 and 25% of control. Sleep time was decreased from 137 ± 12 min (control) to 91 ± 16 and 55 ± 5 min (low and high L-lactate, respectively). D-mannitol did not alter GHB TK/TD and did not alter L-lactate's effects on GHB TK/TD. L-lactate, but not D-mannitol, inhibited GHB uptake, and increased GHB efflux from RBE4 cells. CONCLUSIONS: L-lactate decreases plasma and brain ECF concentrations of GHB, decreasing sedative/hypnotic effects.
Authors:
Samuel A Roiko; Nisha Vijay; Melanie A Felmlee; Marilyn E Morris
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-15
Journal Detail:
Title:  Pharmaceutical research     Volume:  -     ISSN:  1573-904X     ISO Abbreviation:  Pharm. Res.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences, State University of New York, Buffalo, Buffalo, New York, 14214-8033, USA.
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