Effects of Sevelamer Hydrochloride and Calcium Acetate on the Oral Bioavailability of Ciprofloxacin

Michael B. Kays, Brian R. Overholser, Bruce A. Mueller, Sharon Moe, Kevin M. Sowinski

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Background: The oral bioavailability of ciprofloxacin is significantly decreased when administered with calcium carbonate. Sevelamer hydrochloride is a phosphate-binding cationic polymer that is devoid of calcium. The authors conducted a 3-way, randomized, crossover study to determine the effects of sevelamer hydrochloride and calcium acetate on the relative oral bioavailability of ciprofloxacin. Methods: Fifteen healthy volunteers were assigned randomly to receive each of the following oral regimens: ciprofloxacin 750 mg, alone (Arm A); ciprofloxacin 750 mg plus 7 sevelamer hydrochloride 403 mg capsules (Arm B); ciprofloxacin 750 mg plus 4 calcium acetate 667 mg tablets (Arm C). Serial blood and urine samples were obtained over 24 hours, and ciprofloxacin concentrations were determined by high-performance liquid chromatography. Pharmacokinetic data were analyzed using noncompartmental methods, and maximum serum concentration (Cmax) and area under the serum concentration time curve from 0 to infinity (AUC0-∞) were tested for bioequivalence after log transformation of the data. The relative oral bioavailability of ciprofloxacin was calculated as AUC0-∞ , Arm B or Arm C/AUC0-∞, Arm A. Results: The Cmax and AUC0-∞ of ciprofloxacin were significantly decreased when administered concomitantly with sevelamer hydrochloride or calcium acetate (P <0.05), and bioequivalence was not achieved for either parameter. The relative oral bioavailability of ciprofloxacin was decreased by 48% with sevelamer hydrochloride and 51% with calcium acetate (P <0.05). Conclusion: The relative oral bioavailability of ciprofloxacin is significantly decreased when administered with sevelamer hydrochloride or calcium acetate. Concomitant administration of these drugs may decrease clinical efficacy and promote bacterial resistance to ciprofloxacin.

Original languageEnglish (US)
Pages (from-to)1253-1259
Number of pages7
JournalAmerican Journal of Kidney Diseases
Volume42
Issue number6
DOIs
StatePublished - Dec 2003
Externally publishedYes

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calcium acetate
Ciprofloxacin
Biological Availability
Therapeutic Equivalency
Sevelamer

Keywords

  • Bioavailability
  • Calcium acetate
  • Ciprofloxacin
  • Sevelamer hydrochloride

ASJC Scopus subject areas

  • Nephrology

Cite this

Effects of Sevelamer Hydrochloride and Calcium Acetate on the Oral Bioavailability of Ciprofloxacin. / Kays, Michael B.; Overholser, Brian R.; Mueller, Bruce A.; Moe, Sharon; Sowinski, Kevin M.

In: American Journal of Kidney Diseases, Vol. 42, No. 6, 12.2003, p. 1253-1259.

Research output: Contribution to journalArticle

Kays, Michael B. ; Overholser, Brian R. ; Mueller, Bruce A. ; Moe, Sharon ; Sowinski, Kevin M. / Effects of Sevelamer Hydrochloride and Calcium Acetate on the Oral Bioavailability of Ciprofloxacin. In: American Journal of Kidney Diseases. 2003 ; Vol. 42, No. 6. pp. 1253-1259.
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AU - Overholser, Brian R.

AU - Mueller, Bruce A.

AU - Moe, Sharon

AU - Sowinski, Kevin M.

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N2 - Background: The oral bioavailability of ciprofloxacin is significantly decreased when administered with calcium carbonate. Sevelamer hydrochloride is a phosphate-binding cationic polymer that is devoid of calcium. The authors conducted a 3-way, randomized, crossover study to determine the effects of sevelamer hydrochloride and calcium acetate on the relative oral bioavailability of ciprofloxacin. Methods: Fifteen healthy volunteers were assigned randomly to receive each of the following oral regimens: ciprofloxacin 750 mg, alone (Arm A); ciprofloxacin 750 mg plus 7 sevelamer hydrochloride 403 mg capsules (Arm B); ciprofloxacin 750 mg plus 4 calcium acetate 667 mg tablets (Arm C). Serial blood and urine samples were obtained over 24 hours, and ciprofloxacin concentrations were determined by high-performance liquid chromatography. Pharmacokinetic data were analyzed using noncompartmental methods, and maximum serum concentration (Cmax) and area under the serum concentration time curve from 0 to infinity (AUC0-∞) were tested for bioequivalence after log transformation of the data. The relative oral bioavailability of ciprofloxacin was calculated as AUC0-∞ , Arm B or Arm C/AUC0-∞, Arm A. Results: The Cmax and AUC0-∞ of ciprofloxacin were significantly decreased when administered concomitantly with sevelamer hydrochloride or calcium acetate (P <0.05), and bioequivalence was not achieved for either parameter. The relative oral bioavailability of ciprofloxacin was decreased by 48% with sevelamer hydrochloride and 51% with calcium acetate (P <0.05). Conclusion: The relative oral bioavailability of ciprofloxacin is significantly decreased when administered with sevelamer hydrochloride or calcium acetate. Concomitant administration of these drugs may decrease clinical efficacy and promote bacterial resistance to ciprofloxacin.

AB - Background: The oral bioavailability of ciprofloxacin is significantly decreased when administered with calcium carbonate. Sevelamer hydrochloride is a phosphate-binding cationic polymer that is devoid of calcium. The authors conducted a 3-way, randomized, crossover study to determine the effects of sevelamer hydrochloride and calcium acetate on the relative oral bioavailability of ciprofloxacin. Methods: Fifteen healthy volunteers were assigned randomly to receive each of the following oral regimens: ciprofloxacin 750 mg, alone (Arm A); ciprofloxacin 750 mg plus 7 sevelamer hydrochloride 403 mg capsules (Arm B); ciprofloxacin 750 mg plus 4 calcium acetate 667 mg tablets (Arm C). Serial blood and urine samples were obtained over 24 hours, and ciprofloxacin concentrations were determined by high-performance liquid chromatography. Pharmacokinetic data were analyzed using noncompartmental methods, and maximum serum concentration (Cmax) and area under the serum concentration time curve from 0 to infinity (AUC0-∞) were tested for bioequivalence after log transformation of the data. The relative oral bioavailability of ciprofloxacin was calculated as AUC0-∞ , Arm B or Arm C/AUC0-∞, Arm A. Results: The Cmax and AUC0-∞ of ciprofloxacin were significantly decreased when administered concomitantly with sevelamer hydrochloride or calcium acetate (P <0.05), and bioequivalence was not achieved for either parameter. The relative oral bioavailability of ciprofloxacin was decreased by 48% with sevelamer hydrochloride and 51% with calcium acetate (P <0.05). Conclusion: The relative oral bioavailability of ciprofloxacin is significantly decreased when administered with sevelamer hydrochloride or calcium acetate. Concomitant administration of these drugs may decrease clinical efficacy and promote bacterial resistance to ciprofloxacin.

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KW - Ciprofloxacin

KW - Sevelamer hydrochloride

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