• Theresa V Nguyen, David Fleisher, and David E Smith.
• Department of Pharmaceutical Sciences, The University of Michigan, Ann Arbor, Michigan 48109-1065, USA. tvnguyen@umich.edu
• Pharm. Res. 2007 Aug 1; 24 (8): 1538-43.

PurposeThe objective of this study was to evaluate the in vivo consequences of glycyl-glutamate coadministration on gabapentin oral absorption.MethodsRats were administered gabapentin (10 mg/kg plus radiotracer) by gastric gavage, in the absence and presence of dipeptides, and by intravenous administration. Serial blood samples were obtained over 6 h and the pharmacokinetics of gabapentin were determined by noncompartmental analysis.ResultsGlycyl-glutamate coadministration increased the Cmax of gabapentin by 86% as compared to gabapentin alone. In agreement, the oral absorption of gabapentin, relative to the intravenous dose, was 79% after glycyl-glutamate loading but only 47% when drug was administered alone. However, when glycyl-sarcosine was added to the orally administered admixture of gabapentin plus glycyl-glutamate, values for Cmax and AUC(0-6 h) reverted back to that of control. In contrast, the tmax and terminal half-life of gabapentin did not change after oral dosing for all treatments.ConclusionsThese findings are unique in demonstrating that under physiologic, in vivo conditions, the luminal presence of glycyl-glutamate could dramatically enhance the Cmax and AUC(0-6 h) of gabapentin. The results are consistent with previous in situ intestinal perfusion studies in rat, and establish a functional interaction between the activities of PEPT1 and amino acid exchangers.

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