Impairment of ciprofloxacin absorption by calcium polycarbophil.
The effect of calcium polycarbophil on the absorption of ciprofloxacin, a broad-spectrum antibacterial agent, was evaluated in an in vitro and in vivo study. In the in vitro study, the release of ciprofloxacin from the cellulose membrane in the presence or absence of metal cations was measured using the dissolution test procedure. In the in vivo study, male ST Wistar rats and male volunteers were employed. First, 20 mg/kg of ciprofloxacin alone (Rat Study 1) or 20 mg/kg of ciprofloxacin in combination with 64 mg/kg of calcium chloride (Rat Study 2) was administered orally to 3 rats. Second, a volunteer study was employed and a randomized crossover design with twophases was used. In onephase, volunteers received 400 mg of ciprofloxacin alone (Study 1); in the other phase, they received 400 mg of ciprofloxacin and 1200 mg of fine calcium polycarbophil granules concomitantly (Study 2). The plasma and serum concentrations of ciprofloxacin were measured by high-performance liquid chromatography. The release of ciprofloxacin from the cellulose membrane in the presence of aluminum, calcium, or iron ions was slower than that in the absence of these metal ions. The AUC0-4 and Cmax in Rat Study 2 were lower than those respective values in Rat Study 1. AUC0-4 was approximately 60% lower in Rat Study 2 than Rat Study 1. In the volunteer study, the AUC0-12 and Cmax in Study 2 were lower than those respective values in Study 1. In particular, AUC0-12 was approximately 50% lowerin Study 2 than in Study 1. These findings suggest that when ciprofloxacin and calcium polycarbophil were coadministered concomitantly, a decrease of ciprofloxacin absorption was observed, and this action was caused by the formation of chelate complexes. Therefore, it seems clear that we should avoid the concomitant administration of ciprofloxacin and calcium polycarbophil.
Kato
Ryuji
R
Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
Ueno
Kazuyuki
K
Imano
Hideki
H
Kawai
Masayuki
M
Kuwahara
Shiro
S
Tsuchishita
Yoshimasa
Y
Yonezawa
Emi
E
Tanaka
Kazuhiko
K
D000042:Absorption; D000180:Acrylic Resins / Q000737:chemistry*; D000328:Adult; D000534:Alum Compounds / Q000737:chemistry; D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002118:Calcium / Q000737:chemistry; D002122:Calcium Chloride / Q000737:chemistry; D002400:Cathartics / Q000737:chemistry*; D002412:Cations; D002482:Cellulose / Q000737:chemistry; D002614:Chelating Agents / Q000737:chemistry; D002939:Ciprofloxacin / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions; D005296:Ferrous Compounds / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D051381:Rats; D017208:Rats, Wistar
D000180:Acrylic Resins; D000534:Alum Compounds; D000890:Anti-Infective Agents; D002400:Cathartics; D002412:Cations; D002614:Chelating Agents; D005296:Ferrous Compounds; D008567:Membranes, Artificial; C041524:aluminum sulfate; C020748:ferrous sulfate; D002939:Ciprofloxacin; C030312:calcium polycarbophil; D002482:Cellulose; D002122:Calcium Chloride; D002118:Calcium