Effect of a high-protein meal on gabapentin pharmacokinetics

Gidal, Barry E.; Maly, Melissa M.; Budde, Jim; Lensmeyer, Gary L.; Pitterle, Michael E.; Jones, John C.

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Volume 23, Issue 1 , Pages 71-76, February 1996

Effect of a high-protein meal on gabapentin pharmacokinetics

Barry E. Gidal
- Corresponding author. School of Pharmacy and Department of Neurology, University of Wisconsin-Madison, 425 N. Charter Street, Madison, WI 53706, USA. Tel.: (608) 262-3280; fax: (608) 265-5421.
- University of Wisconsin, School of Pharmacy, Madison, WI, USA
- University of Wisconsin, Department of Neurology, Madison, WI, USA
Melissa M. Maly
- University of Wisconsin, Department of Neurology, Madison, WI, USA
Jim Budde
- University of Wisconsin, School of Pharmacy, Madison, WI, USA
Gary L. Lensmeyer
- University of Wisconsin, Department of Laboratory Medicine, Madison, WI, USA
Michael E. Pitterle
- University of Wisconsin, School of Pharmacy, Madison, WI, USA
John C. Jones
- University of Wisconsin, Department of Neurology, Madison, WI, USA

Received 17 April 1995; received in revised form 15 July 1995; accepted 20 July 1995.

Abstract

The anticonvulsant gabapentin is transported across biological membranes via the l-amino acid transport system (System-L). Absorption of gabapentin is saturable, and in-vitro data have previously demonstrated that both l-leucine and l-phenylalanine may compete with the intestinal transport of gabapentin. The purpose of this study therefore was to determine whether a high-protein meal would interfere with gabapentin absorption. Ten healthy volunteers received in a randomized, cross-over design, a single 600-mg dose of gabapentin in the fasting state and after a high-protein meal consisting of 80 gm total protein (4.1 g phenylalanine, 8.2 g leucine and 4.2 g isoleucine), 52 g carbohydrate, and 9 g fat. Plasma gabapentin concentrations were measured by HPLC at baseline, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 30 h. Calculated pharmacokinetic parameters included C_max, T_max, AUC and . In addition, a pharmacodynamic assessment (using visual analog scales) of gabapentin-related adverse effects was performed at 2 h post drug ingestion and was compared between study phases. Statistical analysis included Student's t-test for paired data, with significance assigned at P < 0.05. C_max was significantly increased by 36% (3.87 ± 1.15 vs 5.28 ± .97 μg/ml, P = 0.002), and T_max tended to be shorter (3.9 ± 1.8 vs 2.8 ± .35 h, P = 0.10), after the high-protein meal. Although AUC was increased by 11%, this did not achieve statistical significance. Despite significantly higher plasma concentrations at 2 h, subjects reported significantly fewer adverse effects after the high-protein meal.

Potential mechanisms to explain these unexpected findings may be that the large amino acid load delivered with the high-protein meal enhanced gabapentin absorption via trans-stimulation, the process by which acutely increased intestinal luminal amino acid concentrations result in an acute up regulation in System-L activity. Conversely, the decrease in perceived adverse CNS effects of gabapentin following the high-protein meal may reflect CNS competition for System-L transport.

Keywords: Gabapentin, Pharmacokinetics, Drug-nutrient interaction, L-amino acid transport system

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