Neural modulation of cephalexin intestinal absorption through the di- and tripeptide brush border transporter of rat jejunum in vivo

Intestinal absorption of beta-lactamine antibiotics (e.g., cefixime and cep halexin) has been shown to proceed through the dipeptide carrier system. In a previous study, nifedipine (NFP), an L-type calcium channel blocker, enh anced the absorption of cefixime in vivo but not in vitro, and it was sugge sted that neural mechanisms might be involved in the effect of NFP. The aim of the present study was to assess the involvement of the nervous system o n the intestinal absorption of cephalexin (CFX). To investigate this, we us ed a single-pass jejunal perfusion technique in rats. NFP and diltiazem enh anced approximately 2-fold the plasma levels of CFX in treated rats versus untreated controls. NFP also increased approximately 2-fold the CFX level i n portal plasma and increased urinary excretion of CFX, thus indicating tha t CFX did effectively increase CFX intestinal absorption. Perfusing high co ncentrations of dipeptides in the jejunal lumen competitively reduced CFX a bsorption and inhibited the enhancement of CFX absorption produced by NFP. Hexamethonium and lidocaine inhibited the effect of NFP, whereas atropine, capsaicin, clonidine, and isoproterenol enhanced CFX absorption by the same order of magnitude as NFP. Thus, complex neural networks can modulate the function of the intestinal di- and tripeptide transporter. Sympathetic nora drenergic fibers, intestinal sensory neurons, and nicotinic synapses are in volved in the increase of CFX absorption produced by NFP.