Impact of Concomitant Antacid Administration on Gabapentin Plasma Exposure and Oral Bioavailability in Healthy Adult Subjects

Summary:The aim of this open-label, randomized, and 3-period crossover study was to evaluate the influences of concomitant antacid administration on the plasma disposition, intestinal absorption, and urinary excretion of gabapentin in humans. Gabapentin (200 mg) was orally administered alone, with 1g magnesium oxide (MgO), or with 20 mg omeprazole to 13 healthy adult subjects. Oral bioavailability (BA) of gabapentin was estimated by 24-h urine collection. The Cmax, Tmax and AUC0 -∞ of gabapentin + MgO were significantly lower than that of gabapentin alone (by 33%, 36% and 43%, respectively) and gabapentin + omeprazole (by 29%, 46% and 40%, respectively). In contrast, no significant differences were observed in the plasma disposition parameters of gabapentin between the treatments with and without omeprazole. The gabapentin BA in the MgO treatment was significantly lower, by 32% and 39%, compared to the gabapentin alone and with omeprazole treatment, respectively. There was no significant difference in the gabapentin BA between the gabapentin alone and with omeprazole treatment. Concomitant MgO and omeprazole did not affect the renal clearance of gabapentin. In conclusion, concomitant MgO decreased the gabapentin exposure through the reduction of intestinal absorption extent and rate. This reduction may be independent of the suppression of gastrointestinal acidification caused by antacids.