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Received for publication January 10, 2005.
Revised February 12, 2005.
Accepted for publication February 17, 2005.
-Hydroxybutyric Acid in Rats: Increasing Renal Elimination as a Detoxification Strategy
Intoxication with 
-hydroxybutyric acid (GHB) is associated with coma, seizure and death; treatment of overdoses is symptomatic. The objectives of this investigation were to characterize the renal clearance and total clearance of GHB in rats, and to evaluate potential strategies for increasing the elimination of GHB following drug overdoses. GHB was administered by iv infusion at low (108mg/h/kg), medium (128mg/h/kg) or high (208mg/h/kg) doses. Crossover studies were performed under steady-state conditions using the medium dose in the absence or presence of L-lactate, pyruvate, D-mannitol, sodium bicarbonate or normal saline. GHB in plasma and urine samples was assayed using LC/MS/MS. Infusion of the low, medium and high doses of GHB produced steady state plasma concentrations of 0.22±0.04, 0.43±0.05 and 0.68±0.11 mg/ml. The renal clearance of the medium (51.8±13.0ml/h/kg) and high (97.1±43.1ml/h/kg) doses were significantly higher than that of the low dose (14.9±5.1ml/h/kg), while the total clearance values were significantly lower than that of the low dose. The renal clearance was significantly increased by the concomitant administration of L-lactate, pyruvate, D-mannitol or sodium bicarbonate with GHB, but not altered by normal saline. The total and metabolic clearance values were significantly increased by all treatments except normal saline. Overall, our results indicated that the renal clearance of GHB is dose-dependent, involving capacity-limited reabsorption. Monocarboxylate transport inhibitors, osmotic diuresis using D-mannitol or the administration of sodium bicarbonate can increase the renal and total clearances of GHB. The approaches used in this investigation may offer potential detoxification strategies for the treatment of GHB overdoses.
Key words:
Gamma-hydroxybutyrate, detoxification, drug overdose, monocarboxylate transporter, renal clearance, renal reabsorption
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