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Active intestinal elimination of ciprofloxacin in rats: modulation by different substrates
Author(s) -
Dautrey S,
Felice K,
Petiet A,
Lacour B,
Carbon C,
Farinotti R
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702703
Subject(s) - organic anion transporting polypeptide , ciprofloxacin , pharmacology , sparfloxacin , chemistry , verapamil , quinidine , organic anion transporter 1 , azlocillin , intestinal permeability , p glycoprotein , transporter , organic cation transport proteins , efflux , medicine , endocrinology , antibiotics , biology , biochemistry , ofloxacin , genetics , piperacillin , organic chemistry , pseudomonas aeruginosa , bacteria , multiple drug resistance , gene , calcium
Two in vivo models, in the rat, were used to investigate, in the presence of different substrates, the overall and net intestinal elimination of ciprofloxacin: an open‐intestinal perfusion model and an intestinal loop model respectively. In the presence of quinidine, verapamil and cyclosporin (substrates of the P‐glycoprotein (P‐gp)), plasma AUCs of ciprofloxacin were 1.5–2 fold increased, while biliary clearance (1.5–2 fold), intestinal overall and net clearances (2–4 fold and 1.5–8 fold respectively) decreased. The weak effect obtained with cyclosporin as compared to verapamil and especially quinidine, suggests, for ciprofloxacin, the existence of transport systems distinct from the P‐gp, as the OCT1 transporter which could be inhibited by quinidine. With cephalexin and azlocillin, two β‐lactam antibiotics, plasma AUCs of ciprofloxacin increased and biliary and intestinal overall clearances decreased in a similar fashion (1.3–2 fold), suggesting the involvement of organic anion and/or cation transporters. In the presence of structural analogues, the effect was dependent on the compound administered: Sparfloxacin had no effect on intestinal clearance of ciprofloxacin. In contrast, with pefloxacin, overall intestinal clearance of ciprofloxacin was decreased and net intestinal clearance increased. The specificity of ciprofloxacin intestinal transport appears to be different from P‐gp as outlined by the lack of competition with sparfloxacin, a P‐gp substrate. Ciprofloxacin intestinal elimination seems to be mediated by organic anion and/or cation transporters and a mechanism sensitive to quinidine and verapamil.British Journal of Pharmacology (1999) 127 , 1728–1734; doi: 10.1038/sj.bjp.0702703