Effects of L-lactate and D-mannitol on gamma-hydroxybutyrate toxicokinetics and toxicodynamics in rats.

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Qi WangMarilyn E Morris

Abstract

Overdoses of gamma-hydroxybutyrate (GHB), a drug of abuse, result in coma, respiratory arrest, and death. The objective of this study was to evaluate a potential GHB detoxification strategy by inhibiting the monocarboxylate transporter (MCT)-mediated renal reabsorption of GHB in rats, using the MCT substrate L-lactate. The use of the osmotic diuretic D-mannitol alone or combined with L-lactate was also explored. GHB (208 mg/h/kg) was infused i.v. for 3 h in the absence or presence of L-lactate (60.5, 121, and 302.5 mg h(-1) kg(-1)), D-mannitol (0.5 g/kg), or L-lactate (60.5 mg h(-1) kg(-1)) combined with D-mannitol (0.5 g/kg). GHB in plasma and urine samples was determined along with blood pH, electrolytes, glucose, and L-lactate. Administration of L-lactate, or the combination of L-lactate and D-mannitol, but not D-mannitol alone, significantly increased the renal and total clearances of GHB in rats. Blood pH and electrolyte concentrations exhibited small changes with GHB, GHB/lactate, and GHB/mannitol treatments, although most values remained within their normal range. The concomitant administration of lactated Ringer's solution (28 mM L-lactate) at 300 mul/min with mannitol (0.5 g/kg) resulted in a significant increase in GH...Continue Reading

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May 19, 2006·The Journal of Pharmacology and Experimental Therapeutics·Qi WangMarilyn E Morris

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Citations

Dec 3, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Wing Ki LamMarilyn E Morris
Oct 7, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Bridget L MorseMarilyn E Morris
Oct 25, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Samuel A RoikoMarilyn E Morris
Mar 11, 2010·The Journal of Pharmacology and Experimental Therapeutics·Melanie A FelmleeMarilyn E Morris
Feb 9, 2013·The Journal of Pharmacology and Experimental Therapeutics·Bridget L Morse, Marilyn E Morris
Jul 1, 2017·The American Journal of Drug and Alcohol Abuse·Bridget L MorseMarilyn E Morris
Dec 28, 2017·The AAPS Journal·Melanie A FelmleeMarilyn E Morris
Jul 3, 2013·The Journal of Pharmacology and Experimental Therapeutics·Bridget L Morse, Marilyn E Morris
May 20, 2015·The Journal of Pharmacology and Experimental Therapeutics·Louise ThiesenPetrine Wellendorph
Jan 9, 2021·The AAPS Journal·Melanie A FelmleeMarilyn E Morris
May 9, 2021·The Journal of Pharmacology and Experimental Therapeutics·Vivian Rodriguez-Cruz, Marilyn E Morris

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