Elimination of Lomefloxacin in Rat Intestinal Loop

H, Vergin; Metz, Richard; Nau, R.; Kinzig, Martina; Sörgel, Fritz

doi:10.2165/00003495-199300453-00081

Cited by 5 publications

(6 citation statements)

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“…Fluoroquinolone elimination has been demonstrated to occur in the small bowels of rats (9,11,16), in human Caco-2 intestinal cells grown as monolayers (10), and in isolated rabbit small intestinal mucosal segments mounted in Grass chambers (5). This is however the first demonstration of elimination of ciprofloxacin beyond the ileocecal valve.…”

Section: Discussionmentioning

confidence: 91%

Intestinal elimination of ciprofloxacin in rabbits

Ramon

Dautrey

Farinoti

et al. 1994

Antimicrob Agents Chemother

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The intestinal transepithelial elimination of ciprofloxacin was studied in a rabbit model. Jejunal, ileal, and cecal segments along with their intact blood vessels were isolated and perfused, and their contents were collected over a 120-min period following administration of a single parenteral dose of 27 mg of ciprofloxacin per kg of body weight. The intestinal elimination rates of ciprofloxacin were 0.126 ± 0.084, 0.235 ± 0.22, and 0.11 ± 0.084 ,ug * min-'1 cm 2 for the jejunal, ileal, and cecal segments, respectively. The calculated fractions of ciprofloxacin eliminated were 3.3 mg from the jejunum and 13.8 mg from the ileum, representing 19%o of the administered dose. Additional amounts of 2.5 to 3.7 mg or 4.9 to 7.3% of the administered dose were eliminated from the cecum. Elimination was probably not due to a passive diffusion process but rather due to an active transepithelial transport. This intestinal elimination pattern of ciprofloxacin may explain the unusual activity of the fluoroquinolones in modifying the intestinal flora.The intestine is considered an important pathway in eliminating ciprofloxacin and other fluoroquinolones. In human volunteers, 17.8% of an intravenous "'C-labelled ciprofloxacin dose (107 mg) and 32.5% of an oral dose (259 mg) were recovered from feces over a 5-day collection period (the M2 and M3 ciprofloxacin metabolites recovered from feces were only 2.6 and 12.5% of the intravenous and oral doses, respectively) (1). Orally administered activated charcoal, which binds fluoroquinolones, was found by Mahr et al. (8) and Sorgel et al.(15) to decrease renal excretion and increase total and nonrenal clearance of ciprofloxacin and other fluoroquinolones significantly, suggesting that the intestinal tract was an important excretory organ for fluoroquinolones. Since the amount of ciprofloxacin excreted in bile is limited to only 1 to 3% of the administered dose (15, 19) and concentrations in feces reach 185 to 2,220 pug/g (2, 12), the transepithelial route is probably responsible for ciprofloxacin elimination in the intestine.In rats, the jejunum seems to be the most important intestinal segment, eliminating ca. 3.8 to 5.8% of a systemically administered ciprofloxacin dose over a 90-min period (11). The process is fast, since radiolabelled ciprofloxacin administered intravenously was found in the lower intestinal tract soon after its administration at a distance far too long to be accounted for by biliary secretion (13). No information is available regarding the elimination of ciprofloxacin in rats or other laboratory animals in sites distal to the ileocecal valve.In the present study, we investigated whether the elimination of ciprofloxacin in rabbits following administration of a single intravenous dose occurs in jejunal and ileal segments only or whether elimination occurs in cecal segments as well. MATERIALS AND METHODSThe antibiotic used was ciprofloxacin hydrochloride (Bayer AG, Leverkusen, Germany animals were anesthetized with ketamine (10 ml of a 0.5% solution) (Parke-Davis, A...

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Section: Discussionmentioning

confidence: 91%

Intestinal elimination of ciprofloxacin in rabbits

Ramon

Dautrey

Farinoti

et al. 1994

Antimicrob Agents Chemother

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“…In humans, temafloxacin, sparfloxacin, and fleroxacin show significant fecal elimination (12,33). In rats, lomefloxacin is significantly eliminated by the intestine, and this is not influenced by probenecid, a substrate of the anionic transporter (8,38). In rats, 7% of a parenterally administered ciprofloxacin dose is eliminated via the intestine, mostly the jejunum (28).…”

Section: Downloaded Frommentioning

confidence: 99%

“…Verapamil and other fluoroquinolones reduced ciprofloxacin secretion to various degrees (13). Vergin et al (38) observed passive elimination of lomefloxacin by the rat intestine, but this was based only on the lack of effect of probenecid (a ligand of the renal dianionic transporter) on lomefloxacin elimination. Huneau et al (20) observed a net secretory flux of sparfloxacin in the rabbit ileum.…”

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confidence: 99%

Intestinal elimination of ofloxacin enantiomers in the rat: evidence of a carrier-mediated process

Rabbaa

Dautrey

Colas-Linhart

et al. 1996

Antimicrob Agents Chemother

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The aim of this work was to examine the mechanism involved in intestinal elimination of the two optical isomers of ofloxacin in the rat. An intestinal segment was isolated in situ and perfused with saline, while drug solution was administered via the carotid artery. Blood samples and intestinal effluents were collected and analyzed by a high-performance liquid chromatography method. We observed saturable and stereoselective intestinal elimination of the ofloxacin enantiomers. The elimination process favored the R-(+) form of the molecule. After a parenteral dose of 20 mg of racemic ofloxacin per kg of body weight, intestinal clearances were 0.23 +/- 0.03 versus 0.30 +/- 0.03 ml/min for S-(-)- and R-(+)-ofloxacin, respectively. Ciprofloxacin and pefloxacin interfered with ofloxacin elimination and significantly reduced the intestinal clearance of S-(-)- and R-(+)-ofloxacin. With concomitant ciprofloxacin, intestinal clearances became 0.13 +/- 0.02 versus 0.17 +/- 0.03 ml/min and 0.14 +/- 0.01 versus 0.19 +/- 0.05 ml/min with pefloxacin for S-(-)- and R-(+)-ofloxacin, respectively. Those findings argue for the presence of a common transport system in the rat intestine with variable affinities for fluoroquinolones. In addition, verapamil and quinidine, two P-glycoprotein blockers, significantly reduced the intestinal elimination of both ofloxacin isomers (with concomitant verapamil, intestinal clearances were 0.12 +/- 0.02 versus 0.18 +/- 0.03 ml/min for S-(-)- and R-(+)-ofloxacin, respectively, while with concomitant quinidine, values were 0.18 +/- 0.01 versus 0.23 +/- 0.01 ml/min without modifying their areas under the concentration-time curve in serum. Similar results were found with another fluoroquinolone, ciprofloxacin, in previous work. P-glycoprotein appears to be involved in the intestinal elimination of fluoroquinolones in rats. The characterization of fluoroquinolone intestinal elimination has significant clinical relevance for the better evaluation of the influence of this secretory pathway on antibiotic efficacy and selection of resistant bacteria within the intestinal flora.

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“…The quinolone antibacterials have emerged as an area of immense interest because of their broad spectrum of in vitro activity and their in vivo chemotherapeutic efficiency. [3][4][5][6] However, the current quinolones suffer from some drawbacks such as limited activities against a number of clinically important Gram positive such as Streptococcus pneumonia, Streptococcus pyrogens, Staphylococcus aureus and Enterococcus, low activity against anaerobes and increasing quiolones resistance among many pathogens. 7 In view of the above, the design and synthesis of newer antimicrobials is an area of immense significance and continues to attract the attention of increasing number of medicinal chemists.…”

Section: Introductionmentioning

confidence: 99%