Comparative pharmacokinetics of ciprofloxacin and temafloxacin in humans: A review

Sörgel, Fritz; Naber, Kurt G.; Kinzig, Martina; Mahr, G.; Muth, P.

doi:10.1016/0002-9343(91)90312-l

Cited by 42 publications

(24 citation statements)

References 53 publications

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“…Previous studies have highlighted the importance of active efflux transporters in the secretion of ciprofloxacin and other fluoroquinolones into the intestinal lumen (Cavet et al, 1997;Lowes and Simmons, 2002), a clinically important route for elimination (Sörgel et al, 1989(Sörgel et al, , 1991. We have confirmed that murine bcrp1 mediates active efflux of ciprofloxacin across the apical membrane of bcrp1-overexpressing MDCKII cell monolayers, which showed a significant increase in secretion relative to that of wild-type cells .…”

Section: Discussionsupporting

confidence: 77%

“…In vivo it displays variable oral bioavailability of between 50 and 80% (Sörgel et al, 1989a). Ciprofloxacin plasma clearance in vivo is predominantly renal (Jaehde et al, 1989;Rohwedder et al, 1990), but it is also subject to intestinal elimination (Sörgel et al, 1989b(Sörgel et al, , 1991 without undergoing significant metabolism (Sörgel et al, 1989b). The intestinal elimination pathway becomes increasingly important for patients with reduced renal function (Rohwedder et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

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Intestinal Ciprofloxacin Efflux: The Role of Breast Cancer Resistance Protein (ABCG2)

Haslam¹,

Wright²,

O’Reilly³

et al. 2011

Drug Metab Dispos

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ABSTRACT:Intestinal secretory movement of the fluoroquinolone antibiotic, ciprofloxacin, may limit its oral bioavailability. Active ATP-binding cassette ( , and verapamil as ABC-selective inhibitors. In addition, the regional variation in secretory capacity was investigated using male Han Wistar rat intestine mounted in Ussing chambers, and the first indicative measurements of ciprofloxacin transport by ex vivo human jejunum were made. Active, Ko143-sensitive ciprofloxacin secretion was observed in bcrp1-MDCKII cell layers, but in low-passage (BCRP-expressing) Caco-2 cell layers only a 54% fraction was Ko143-sensitive. Ciprofloxacin accumulation was lower in MRP4-HEK293 cells than in the parent line, indicating that ciprofloxacin is also a substrate for this transporter. Ciprofloxacin secretion by Caco-2 cell layers was not inhibited by MK571. Secretory flux showed marked regional variability in the rat intestine, increasing from the duodenum to peak in the ileum. Ciprofloxacin secretion was present in human jejunum and was reduced by Ko143 but showed marked interindividual variability. Ciprofloxacin is a substrate for human and rodent BCRP. An additional pathway for ciprofloxacin secretion exists in Caco-2 cells, which is unlikely to be MRP(4)-mediated. BCRP is likely to be the dominant transport mechanism for ciprofloxacin efflux in both rat and human jejunum.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Intestinal Ciprofloxacin Efflux: The Role of Breast Cancer Resistance Protein (ABCG2)

Haslam¹,

Wright²,

O’Reilly³

et al. 2011

Drug Metab Dispos

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“…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.…”

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confidence: 96%

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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“…The intestine has been shown to play an important role as an elimination tissue or absorption barrier. It was reported that at least 10.6% of intravenously administered ciprofloxacin was eliminated by intestinal secretion (Sörgel et al, 1989b(Sörgel et al, , 1991, and temafloxacin showed significant gastrointestinal secretion into feces in humans (Granneman et al, 1991). Dautrey et al (1999) suggested that the pharmacokinetics of ciprofloxacin involved one or more active secretory mechanisms in the intestine in rats.…”

mentioning

confidence: 99%

Pharmacokinetic Role of P-Glycoprotein in Oral Bioavailability and Intestinal Secretion of Grepafloxacin in Vivo

Yamaguchi

Yano

Saya

et al. 2002

J Pharmacol Exp Ther

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The purpose of this study was to clarify the contribution of P-glycoprotein to the bioavailability and intestinal secretion of grepafloxacin and levofloxacin in vivo. Plasma concentrations of grepafloxacin and levofloxacin after intravenous and intraintestinal administration were increased by cyclosporin A, a Pglycoprotein inhibitor, in rats. The total body clearance and volume of distribution at steady state of grepafloxacin were significantly decreased to 60 and 63% of the corresponding control values by cyclosporin A. The apparent oral clearance of grepafloxacin was decreased to 33% of the control, and the bioavailability of grepafloxacin was increased to 95% by cyclosporin A from 53% in the controls. Intestinal clearance of grepafloxacin and levofloxacin were decreased to one-half and one-third of the control, respectively, and biliary clearance of grepafloxacin was also decreased to one-third with cyclosporin A in rats. Intestinal secretion of grepafloxacin in mdr1a/1b (Ϫ/Ϫ) mice, which lack mdr1-type P-glycoproteins, was significantly decreased compared with wild-type mice, although the biliary secretion was similar. Intestinal secretion of grepafloxacin in wild-type mice treated with cyclosporin A was comparable to those in mdr1a/1b (Ϫ/Ϫ) mice with or without cyclosporin A, indicating that cyclosporin A completely inhibited P-glycoprotein-mediated intestinal transport of grepafloxacin. In conclusion, our results indicated that P-glycoprotein mediated the intestinal secretion of grepafloxacin and limited the bioavailability of this drug in vivo.

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Comparative pharmacokinetics of ciprofloxacin and temafloxacin in humans: A review

Cited by 42 publications

References 53 publications

Intestinal Ciprofloxacin Efflux: The Role of Breast Cancer Resistance Protein (ABCG2)

Intestinal Ciprofloxacin Efflux: The Role of Breast Cancer Resistance Protein (ABCG2)

Intestinal elimination of ciprofloxacin in rabbits

Pharmacokinetic Role of P-Glycoprotein in Oral Bioavailability and Intestinal Secretion of Grepafloxacin in Vivo

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