alexa Monocarboxylate Transporter Inhibition with Osmotic Diu
ISSN: 2161-0495

Journal of Clinical Toxicology
Open Access

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Research Article

Monocarboxylate Transporter Inhibition with Osmotic Diuresis Increases γ-Hydroxybutyrate Renal Elimination in Humans: A Proof-of-Concept Study

Marilyn E. Morris1*, Bridget L. Morse1, Gloria J. Baciewicz2, Matthew M. Tessena2, Nicole M. Acquisto3, David J. Hutchinson4 and Robert DiCenzo5

1Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY (Morris and Morse)

2Department of Psychiatry, University of Rochester Medical Center, University of Rochester, Rochester, NY (Baciewicz and Tessena)

3Departments of Pharmacy and Emergency Medicine, University of Rochester Medical Center, University of Rochester, Rochester, NY (Acquisto)

4Department of Pharmacy Practice, School of Pharmacy, St. John Fisher College, Rochester, NY (Hutchinson)

5Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, NY (DiCenzo)

*Corresponding Author:
Marilyn E. Morris
University at Buffalo, 527 Hochstetter Hall Buffalo, NY 14260
Tel: (716) 645-4839
Fax: (716) 645-3693
E-mail: [email protected]

Received Date: October 01, 2011; Accepted Date: November 03, 2011; Published Date: November 10, 2011

Citation: Morris ME, Morse BL, Baciewicz GJ, Tessena MM, Acquisto NM, et al. (2011) Monocarboxylate Transporter Inhibition with Osmotic Diuresis Increases ?-Hydroxybutyrate Renal Elimination in Humans: A Proof-of-Concept Study. J Clinic Toxicol 1:105. doi: 10.4172/2161-0495.1000105

Copyright: © 2011 Morris ME, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

Background and objective: The purpose of the current study was to demonstrate proof-of-concept that monocarboxylate transporter (MCT) inhibition with L-lactate combined with osmotic diuresis increases renal clearance of ?-hydroxybutyrate (GHB) in human subjects. GHB is a substrate for human and rodent MCTs, which are responsible for GHB renal reabsorption, and this therapy increases GHB renal clearance in rats Methods: Ten healthy volunteers were administered GHB orally as sodium oxybate 50 mg/kg (4.5 gm maximum dose) on two different study days. On study day 1, GHB was administered alone. On study day 2, treatment of L-lactate 0.125 mmol/kg and mannitol 200 mg/kg followed by L-lactate 0.75 mmol/kg/hr was administered intravenously 30 minutes after GHB ingestion. Blood and urine were collected for 6 hours, analyzed for GHB, and pharmacokinetic and statistical analyses performed. Results: L-lactate/mannitol administration significantly increased GHB renal clearance compared to GHB alone, 439 vs. 615 mL/hr (P=0.001), and increased the percentage of GHB dose excreted in the urine, 2.2 vs. 3.3% (P=0.021). Total clearance was unchanged. Conclusions: MCT inhibition with L-lactate combined with osmotic diuresis increases GHB renal elimination in humans. No effect on total clearance was observed in this study due to the negligible contribution of renal clearance to total clearance at this low GHB dose. Considering the nonlinear renal elimination of GHB, further research in overdose cases is warranted to assess the efficacy of this treatment strategy for increasing renal and total clearance at high GHB doses.

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