Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Effect of Cimetidine on the Transport of Quinolone Antibiotics in Caco-2 Cell monolayers

  • Kim, Seon-Hwa (Drug MetabolismTeam, Department of Pharmacology, National Institute of Toxicological Research) ;
  • Jung, Seo-Jeong (Center for Food & Drug Anaylsis, Busan KFDA) ;
  • Um, So-Young (Drug MetabolismTeam, Department of Pharmacology, National Institute of Toxicological Research) ;
  • Na, Mi-Ae (Testing & Analysis Team, Daejeon KFDA) ;
  • Choi, Min-Jin (Drug MetabolismTeam, Department of Pharmacology, National Institute of Toxicological Research) ;
  • Chung, Myeon-Woo (Drug MetabolismTeam, Department of Pharmacology, National Institute of Toxicological Research) ;
  • Oh, Hye-Young (Drug MetabolismTeam, Department of Pharmacology, National Institute of Toxicological Research)
  • Published : 2007.06.30
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Abstract

Cimetidine, a substrate for P-glycoprotein (P-gp), is a well known drug interacting with a variety of drugs and results in alteration of pharmacokinetic parameters by concomitant administration. The aim of present study was to investigate whether cimetidine affects the transport of various quinolone antibiotics in human colorectal cancer cell line (Caco-2) system which has been typically used to investigate drug transport via P-gp. The apparent permeability coefficients (P$_{app}$) value of 9 quinolone antibiotics in the co-treatment with cimetidine was examined. Apical to basolateral (AP-to-BL) transport of fleroxacin in the co-treatment with cimetidine was increased to 1.5-fold (p<0.01) compared with that of fleroxacin alone, whereas basolateral to apical (BL-to-AP) transport of fleroxacin was decreased to 0.83-fold significantly (p<0.05). Ofloxacin was decreased to 0.8-fold (p<0.01) and 0.72-fold (p<0.01) significantly in AP-to-BL and BL-to-AP direction, respectively by cimetidine cotreatment. The P$_{app}$ values of gatifloxacin, moxifloxacin, ciprofloxacin and rufloxacin also were changed by cimetidine. These results have a potential that cimetidine influences on the pharmacokinetics of quinolone antibiotics. It suggests that careful drug monitoring and dosage adjustment may be necessary during the co-administration of quinolone antibiotics with cimetidine.

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References

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