Intestinal absorption of gabapentin in rats

Gabapentin (1-aminomethyl-)cyclohexaneacetic acid, Gö 3450, CI-945; CAS 60142-96-3) is a new gamma-aminobutyric acid (GABA) analogous compound that has shown an anticonvulsive effect as well as low toxicity in preclinical and clinical studies. The substance is well absorbed after oral administration and penetrates the blood-brain barrier. The aim of experiments was to study the mechanism of intestinal absorption, the relationship between the absorption rate and the applied concentration and whether the absorption rate differs between different parts of the intestine. For this purpose, isolated intestinal segments of rats (everted sac preparations) were used. Due to the fact that gabapentin is not metabolized in the intestine, its concentration in the mucosal and serosal compartments could be determined by scintillation counting of 3H-gabapentin. The results showed that gabapentin was absorbed by simple diffusion because neither indications for an uphill nor for a carrier-mediated transport could be demonstrated. The absorption rate was linearly related in the concentration range from 0.001 to 100 mmol/l. There was no significant difference between the absorption rate in the three parts of the small intestine at 1 and 10 mmol/l, while the absorption rate was significantly (p less than 0.01) lower in the colon.