Active intestinal elimination of ciprofloxacin in rats: modulation by different substrates

1 Two in vivo models, in the rat, were used to investigate, in the presence of different substrates, the overall and net intestinal elimination of cip rofloxacin: an open-intestinal perfusion model and an intestinal loop model respectively. 2 In the presence of quinidine, verapamil and cyclosporin (substrates of th e P-glycoprotein (P-gp)), plasma AUCs of ciprofloxacin were 1.5-2 fold incr eased, while biliary clearance (1.5-2 fold), intestinal overall and net cle arances (2-4 fold and 1.5-8 fold respectively) decreased. The weak effect o btained with cyclosporin as compared to verapamil and especially quinidine, suggests, for ciprofloxacin, the existence of transport systems distinct f rom the P-gp, as the OCT1 transporter which could be inhibited by quinidine . 3 With cephalexin and azlocillin, two beta-lactam antibiotics, plasma AUCs of ciprofloxacin increased and biliary and intestinal overall clearances de creased in a similar fashion (1.3-2 fold), suggesting the involvement of or ganic anion and/or cation transporters. 4 In the presence of structural analogues, the effect was dependent on the compound administered: Sparfloxacin had no effect on intestinal clearance o f ciprofloxacin. In contrast, with pefloxacin, overall intestinal clearance of ciprofloxacin was decreased and net intestinal clearance increased. 5 The specificity of ciprofloxacin intestinal transport appears to be diffe rent from P-gp as outlined by the lack of competition with sparfloxacin, a P-gp substrate. Ciprofloxacin intestinal elimination seems to be mediated b y organic anion and/or cation transporters and a mechanism sensitive to qui nidine and verapamil.