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

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 (subst...

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Bibliographic Details
Published in:British journal of pharmacology 1999-08, Vol.127 (7), p.1728-1734
Main Authors: Dautrey, S, Felice, K, Petiet, A, Lacour, B, Carbon, C, Farinotti, R
Format: Article
Language:English
Subjects:
Animals
Anti-Infective Agents - pharmacokinetics
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Area Under Curve
Biological and medical sciences
Biological Transport, Active
Chemical Phenomena
Chemistry, Physical
Ciprofloxacin
Ciprofloxacin - pharmacokinetics
experimental models
Intestinal Absorption - physiology
intestinal elimination
intestinal transporters
Intestines - metabolism
Male
Medical sciences
Pharmacology. Drug treatments
P‐glycoprotein
Rats
Rats, Sprague-Dawley
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Summary: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
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0702703