Active intestinal absorption of fluoroquinolone antibacterial agent ciprofloxacin by organic anion transporting polypeptide, Oatp1a5

Abstract

Fluoroquinolone antimicrobial drugs are absorbed efficiently after oral administration despite of their hydrophilic nature, implying an involvement of carrier-mediated transport in their membrane transport process. It has been that several fluoroquinolones are substrates of organic anion transporter polypeptides OATP1A2 expressed in human intestine derived Caco-2 cells. In the present study, to clarify the involvement of OATP in intestinal absorption of ciprofloxacin, the contribution of Oatp1a5, which is expressed at the apical membranes of rat enterocytes, to intestinal absorption of ciprofloxacin was investigated in rats. The intestinal membrane permeability of ciprofloxacin was measured by in situ and the vascular perfused closed loop methods. The disappeared and absorbed amount of ciprofloxacin from the intestinal lumen were increased markedly in the presence of 7,8-benzoflavone, a breast cancer resistance protein inhibitor, and ivermectin, a P-glycoprotein inhibitor, while it was decreased significantly in the presence of these inhibitors in combination with naringin, an Oatp1a5 inhibitor. Furthermore, the Oatp1a5-mediated uptake of ciprofloxacin was saturable with a K m value of 140 mM, and naringin inhibited the uptake with an IC 50 value of 18 mM by Xenopus oocytes expressing Oatp1a5. Naringin reduced the permeation of ciprofloxacin from the mucosal-to-serosal side, with an IC 50 value of 7.5 mM by the Ussing-type chamber method. The estimated IC 50 values were comparable to that of Oatp1a5. These data suggest that Oatp1a5 is partially responsible for the intestinal absorption of ciprofloxacin. In conclusion, the intestinal absorption of ciprofloxacin could be affected by influx transporters such as Oatp1a5 as well as the efflux transporters such as P-gp and Bcrp.

Antitubercular Agent Delamanid and Metabolites as Substrates and Inhibitors of ABC and Solute Carrier Transporters

“…These transporters are sometimes major determinants of the dispositional fate of drugs, including antibiotics commonly used in the treatment of infections (8,9). For example, in the process of absorption into the body, fluoroquinolones and ␤-lactams are predominantly absorbed via organic anion-transporting polypeptides (OATPs) and peptide transporter 1 on the intestinal membrane barrier (8)(9)(10). In contrast, there are several reports that fluoroquinolones absorbed into enterocytes are expelled by the ATP-binding cassette (ABC) drug efflux transporter P-glycoprotein (P-gp; MDR1/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) back into the gut lumen (11).…”

Oral Contraceptives after Bariatric Surgery

“…Early pharmacokinetic research has shown that some fluoroquinolones are absorbed efficiently from the small intestine and transported by organic anion transporting polypeptides (OATPs) [50]. Colin et al [51] investigated adequate moxifloxacine concentrations using a population pharmacokinetic analysis and pharmacokinetic-pharmacodynamic simulations in post-bariatric surgery patients.…”

Structures and Antibacterial Properties of PLA-based Ciprofloxacin Composite Films Deposited by Low-Electron Beam Dispersion

“…Fluoroquinolones were widely used in human and veterinary medicine for the treatment of infectious diseases [5][6][7]. Ciprofloxacin, a fluoroquinolone antibacterial agent [8,9], has a wide range of antibacterial activity, which is highly active against various Gram-positive and Gram-negative bacteria.…”