ELSEVIER Epilepsy Research 23 (1996) 71-76 EPILEPSY RESEARCH Effect of a high-protein meal on gabapentin pharmacokinetics Barry E. Gidal a,b,*, Melissa M. Maly b, Jim Budde a, Gary L. Lensmeyer c, Michael E. Pitterle a, John C. Jones b a University of Wisconsin. School of Pharmacy. Madison. WI. USA , University of Wisconsin. Department of Neurology. Madison. WI. USA c University of Wisconsin Department of Laboratory Medicine. Madison. WI. USA Received 17 April 1995; revised 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 Cma x, Tma x, AUC and Tl/2. 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. Cma ~ was significantly increased by 36% (3.87 -+ 1.15 vs 5.28 + .97/xg/ml, P = 0.002), and Tin, x 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 1I%, 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 mechanism:~ 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-aminoacid transport system 1. Introduction * Corresponding author. School of Pharmacy and Department of Neurology, Unive~ity o1' Wisconsin-Madison,425 N. Charter Street, Madison, WI 53706, USA. Tel.: (608) 262-3280; fax: (608) 265-542I. Gabapentin is a recently released anticonvulsant medication that has demonstrated efficacy in the treatment of complex partial seizures. Gabapentin is 0920-1211/96/$15.00 © 1996 Elsevier Science B.V. All rights reserved SSDI 0920- 12 I 1(95)00051-8