12th International Conference of Pharmaceutical Sciences

Gabapentin (GBP), clinically used to treat neuropathic pain, is mainly eliminated unchanged in urine. Renal active tubular secretion has been suggested to contribute to GBP renal excretion. The aim of the study was to investigate the role of transporters for organic cations (OCTs, OCTNs, and MATEs) on kinetic disposition of GBP and to verify the regulation of these transporters by glycemic control in diabetes. An in vitro study was performed to evaluate the interaction of GBP with OCTs, OCTN1 and MATE transporters stably expressed in human embryonic kidney cells. Clinical studies were performed in patients with neuropathic pain to evaluate the influence of OCTs inhibitor cetirizine (CTZ) and hyperglycemia on GBP kinetic disposition. In the cross-over study, all participants were treated with oral single-dose of 300 mg of GBP or CTZ (20 mg/day) for 5 days and single-dose of GBP on the last day. We found here that GBP is a substrate for renal transporters hMATE, hOCTN1 and hOCT2. The treatment with CTZ and hyperglycemia reduced systemic exposure to GBP, although these changes cannot be explained by the interaction with renal transporters. These data suggest that CTZ and hyperglycemia reduce GBP oral bioavailability by saturation of intestinal absorption processes.