Effects of sevelamer hydrochloride and calcium acetate on the oral bioavailability of ciprofloxacin.
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 (AUC(0- infinity )) were tested for bioequivalence after log transformation of the data. The relative oral bioavailability of ciprofloxacin was calculated as AUC(0- infinity ), Arm B or Arm C/AUC(0- infinity ), Arm A.


RESULTS
The Cmax and AUC(0- infinity ) 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).


CONCLUSIONS
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.
Kays
Michael B
MB
Department of Pharmacy Practice, Purdue University School of Pharmacy and Pharmacal Sciences, Indianapolis, IN, USA, West Lafayette, IN 46202-2879, USA. mkays@iupui.edu
Overholser
Brian R
BR
Mueller
Bruce A
BA
Moe
Sharon M
SM
Sowinski
Kevin M
KM
D000085:Acetates / Q000493:pharmacokinetics / Q000494:pharmacology*; D000284:Administration, Oral; D000328:Adult; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D017610:Calcium Compounds; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D018592:Cross-Over Studies; D003864:Depression, Chemical; D004347:Drug Interactions; D024881:Drug Resistance, Bacterial; D004852:Epoxy Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D011073:Polyamines; D011095:Polyethylenes / Q000493:pharmacokinetics / Q000494:pharmacology*; D000069603:Sevelamer
D000085:Acetates; D000890:Anti-Infective Agents; D017610:Calcium Compounds; D004852:Epoxy Compounds; D011073:Polyamines; D011095:Polyethylenes; D002939:Ciprofloxacin; D000069603:Sevelamer; C120662:calcium acetate