Kinetic study of acamprosate absorption in rat small intestine

Acamprosate (calcium bis acetyl-homotaurine), a homotaurine derivative, a s tructural analogue of gamma-aminobutyric acid tGABA and an upper homologue of taurine, is a relatively new drug used to prevent relapse in weaned alco holics. When administered orally as enteric-coated tablets at relatively hi gh doses, this drug has a bioavailability of about 11%; however, the intest inal absorption mechanism has nor been studied in depth. The present study was therefore planned to characterize the intestinal transport of acamprosa te in the rat and the effect of chronic alcohol treatment on this process, quantifying its kinetic parameters and investigating possible inhibitors. U sing an in vitro technique, acamprosate absorption was measured in the rat intestine from three different groups: alcohol group [fed a liquid diet con taining 5% (w/v) ethanol for 4 weeks], isocaloric pair-fed control, and a s olid diet group. intestinal acamprosate absorption was found to occur mainl y by passive diffusion with a diffusive permeability of 0.213 +/- 0.004 cm/ h in control pair-fed animals, 0.206 +/- 0.001 cm/h in animals receiving ch ronic alcohol treatment, and 0.193 +/- 0.001 cm/h in the solid diet group. inhibition studies showed that at a 10(-3) M acamprosate concentration, som e compounds such as GABA, taurine, proline, and glycine at 40 mM each did n or affect acamprosate transport. Nevertheless, when a lower concentration o f the drug (10(-4) M) was assayed, a significant reduction of acamprosate t ransport in the presence of taurine or GABA 40 mM was found. These results suggest that acamprosate in the rat jejunum, could he transported, in part, by a carrier system. Further experiments using different concentrations of taurine (10, 20, and 80 mM) showed that the maximum inhibition (32%) is ac hieved at 20 mM of taurine. These latter results suggest that acamprosate a nd taurine sharer at least, an intestinal carrier system in rat jejunum. Fr om the above results, it can be concluded that there are probably two pathw ays involved in the intestinal absorption of acamprosate: passive diffusion and mediated transport, with the former being predominant. Moreover, neith er chronic ethanol intake nor the type of diet stems to alter the intestina l absorption of the drug.