Transintestinal Elimination of Ciprofloxacin

Rohwedder, R. W.; Bergan, Tom; Þorsteinsson, Sigurður B.; Scholl, H

doi:10.1159/000238751

Cited by 76 publications

(65 citation statements)

References 6 publications

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“…doses in patients and volunteers are presented in Fig. 1 except for (40) or by direct secretion of parent compound from intestinal mucosa (52). The renal elimination of many antibiotics is enhanced in CF subjects, usually in relation to the increased GFR (21,22 (47).…”

Section: Resultsmentioning

confidence: 99%

Increased oral bioavailability of ciprofloxacin in cystic fibrosis patients

Christensson

Nilsson-Ehle

Ljungberg

et al. 1992

Antimicrob Agents Chemother

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The altered pharmacokinetic properties of, e.g., aminoglycosides in cystic fibrosis patients have to be considered when pulmonary exacerbations are treated. Since reported data on ciprofloxacin, a fluorinated quinolone, are conflicting, we compared intravenous and oral administration in cystic fibrosis patients when treating them for mild symptoms of pulmonary infection. All of the patients were colonized with Pseudomonas species. Ciprofloxacin was administered orally (15 mg/kg of body weight) or intravenously (6 mg/kg) twice a day for at least 10 days during separate treatment periods. Five healthy volunteers received single intravenous and oral doses. Pharmacokinetic evaluations were performed at first dose and at steady state. The results showed that cystic fibrosis patients have increased oral bioavailability of ciprofloxacin (80% in cystic fibrosis patients versus 57% in volunteers) and increased total clearance (688 ml/min in CF patients versus 528 ml/min in volunteers). Our data indicate that the pharmacokinetic properties of ciprofloxacin are altered in cystic fibrosis patients with mild symptoms of pulmonary exacerbations and that the changes most probably are due to cystic fibrosis per se or to the impact of chronic infection.

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Section: Resultsmentioning

confidence: 99%

Increased oral bioavailability of ciprofloxacin in cystic fibrosis patients

Christensson

Nilsson-Ehle

Ljungberg

et al. 1992

Antimicrob Agents Chemother

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“…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%

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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“…Although there is biliary secretion of pefloxacin (biliary level two to five times higher than blood levels), this cannot explain why the concentration in feces is so much higher than in plasma (8). It has been shown, however, that quinolones are secreted in the bowel across the intestinal mucosa (13). This transepithelial elimination probably is an active transport (14).…”

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confidence: 99%

Concentration of pefloxacin in feces during infection prophylaxis in neutropenic patients

Leur

Vollaard

Janssen

et al. 1995

Antimicrob Agents Chemother

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Pefloxacin (400 mg twice daily) was administered orally for infection prophylaxis in neutropenic patients. Diffusible fecal pefloxacin concentration was determined by bioassay during 24 neutropenic periods. The median diffusible fecal pefloxacin concentration was 187 g/g. This concentration was comparable with those found in volunteers following oral and intravenous administration of pefloxacin (400 mg twice daily) (median of 171 and 155 g/g, respectively). From this study, it is concluded that pefloxacin administered orally results in a predictable high diffusible fecal concentration which leads to effective elimination of susceptible aerobic gram-negative bacilli from the colonic flora.Fluorinated carboxyquinolones are widely used for infection prophylaxis in patients with severe neutropenia (2, 4). These agents have a broad spectrum of activity against aerobic gramnegative bacilli (GNB) (including Pseudomonas aeruginosa) and are effective in preventing infections by gram-negative organisms (1,5,7,(10)(11)(12)18).Long-term prophylaxis of infection in patients with neutropenia may be achieved by elimination of potentially pathogenic aerobic flora from the digestive tract (3). In order to be effective, antibiotics used for decontamination of the digestive tract must reach high and predictable concentrations in the bowel (15). It has been suggested that nonabsorbable antimicrobial agents are required for this purpose (4). In volunteers, however, we observed high antimicrobial activity of pefloxacin in feces after oral (almost complete resorption) and intravenous administration of pefloxacin (16,17).In the present study, we investigated the diffusible fecal concentration of pefloxacin and eradication of GNB from feces in neutropenic patients following oral administration. We compare these results with those of similar previous studies in healthy volunteers following oral and intravenous administration (16,17).During 24 periods of chemotherapy-induced neutropenia, prophylactic antibiotics, including pefloxacin (400 mg twice a day [BID] orally), fluconazole (50 mg orally), amphotericin B (450 mg BID orally), and trimethoprim (2%, as nasal ointment), were given to decontaminate the digestive tract.All 13 patients (median age, 51 years; range, 49 to 76 years) were treated for a hematologic malignancy, and median duration of neutropenia (Ͻ500 neutrophils per l) was 16 days (range, 9 to 35). During the prophylaxis, no salads were permitted. Fecal samples were taken at admission and twice weekly to determine the diffusible pefloxacin concentration and to perform viable counts of aerobic GNB.The diffusible fecal concentration of pefloxacin was determined by an agar diffusion method. An undiluted aliquot of feces was put in a well (depth, 5 mm; diameter, 7 mm; volume, 0.77 ml) in a solid medium of Iso-Sensitest agar (300 ml; Oxoid, Basingstoke, United Kingdom) seeded with a strain of Escherichia coli (ATCC 25922). The MIC of pefloxacin for this strain is 0.25 g/ml. The diameters of the inhibition zones were compared with t...

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Transintestinal Elimination of Ciprofloxacin

Cited by 76 publications

References 6 publications

Increased oral bioavailability of ciprofloxacin in cystic fibrosis patients

Increased oral bioavailability of ciprofloxacin in cystic fibrosis patients

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

Concentration of pefloxacin in feces during infection prophylaxis in neutropenic patients

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