Active intestinal elimination of ciprofloxacin in rats: modulation by different substrates.
TL;DR: Ciprofloxacin intestinal elimination seems to be mediated by organic anion and/or cation transporters and a mechanism sensitive to quinidine and verapamil, as well as the existence of transport systems distinct from the P‐gp.
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Abstract: 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
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Intestinal secretion is a major route for parent ivermectin elimination in the rat.
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References
The P-Glycoprotein Efflux Pump: How Does it Transport Drugs?
TL;DR: To date, no studies have unequivocally measured outward pumping of any “MDR drug” from lipid to an aqueous phase, and it is unclear which phenotypic features are due to Pgp, and which could be due to other events caused by chemotherapeutic drug exposure.
230
Role of organic cation transporters in drug absorption and elimination
TL;DR: Current models of transepithelial flux of organic cations in these three tissues are discussed, with particular emphasis placed on the more recent molecular studies that have paved the way for a more complete understanding of the physiological and pharmacological roles of the organic cation transporters.
203
•Journal Article
Active intestinal secretion of the fluoroquinolone antibacterials ciprofloxacin, norfloxacin and pefloxacin; a common secretory pathway?
TL;DR: It is likely that the mechanism of transepithelial secretion involves a common accumulative transport at the basal-lateral membrane followed by facilitated exist across the apical membrane, and may interact with a brush-border carrier for which norfloxacin and ciprofloxACin are poor substrates, enhancing the absorptive flux of this fluoroquinolone.
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Transintestinal elimination of ciprofloxacin.
Rolf Rohwedder,Rolf Rohwedder,Tom Bergan,Tom Bergan,Sigurdur B. Thorsteinsson,Sigurdur B. Thorsteinsson,Hans Joachim Dr. Scholl,Hans Joachim Dr. Scholl +7 more
TL;DR: It is demonstrated that transintestinal elimination of ciprofloxacin serves as an extrarenal safety factor compensating for reduced elimination by the renal route, and it is proposed that elimination by faeces is due primarily to trans gastrointestinal elimination.
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