Absorption of ofloxacin isomers in the rat small intestine

Abstract

Ofloxacin, a chiral fluoroquinolone, possesses two optical isomers. The antibacterial activity of S-(-)-ofloxacin is 8 to 128 times higher than that of R-(+)-ofloxacin. In the rat, a saturable absorption process has been described for racemic ofloxacin. In the present study we investigated the mechanism underlying the in vivo intestinal absorption of ofloxacin enantiomers in the rat. Blood samples were collected from the portal vein. Our results show that the intestinal absorption of ofloxacin isomers is pH dependent, both enantiomers being best absorbed at neutral pH. S-(-)-Ofloxacin seems to have a greater affinity for the intestinal transporter (initial concentrations at 5 min [C(init)] are 0.17 +/- 0.04 and 0.12 +/- 0.03 microg/ml for S-(-)- and R-(+)-ofloxacin, respectively). Dipeptides fail to modify ofloxacin absorption, but amino acids reduce both isomers' absorption (C(init) is reduced by 53 and 33% with glycine for S-(-)- and R-(+)-ofloxacin, respectively, and by 59 and 42% with L-leucine). Gamma amino butyric acid interferes with the absorption of ofloxacin isomers, but less seriously than do amino acids. Furthermore, ofloxacin competes with other fluoroquinolones or P-glycoprotein substrates for a common secretory pathway, resulting in an increased rate of absorption for both ofloxacin isomers; this is probably an indirect result of their reduced efflux from the apical side of intestinal cells.

Pharmacokinetic study of ofloxacin enantiomers in Pagrosomus major by chiral HPLC

“…At the same time, enantioselectivity of the two OFLX enantiomers during elimination was due to the differences in renal clearance. Rabbaa et al (1997) studied the removal mechanism of OFLX enantiomers in the rat intestine, and found that proteins affect the elimination kinetics of the two enantiomers. Our research established the pharmacokinetics of OFLX enantiomers in P. major, and found that they differed from those in humans and rats.…”

Chiral separation of quinolones by liquid chromatography and capillary electrophoresis

“…Hence, special measures are undertaken to isolate individual enantiomers from these enantiomeric mixtures. Frequently, only one enantiomer is pharmaceutically active while the other may be toxic, ballast, or inactive . Therefore, to avoid the toxicities, side effects, and other problems, these antibacterial agents should be administered in the form of pharmaceutically active pure enantiomers.…”

Enantiomeric Separation of Ofloxacin by Nano-Liquid Chromatography Using a Sulfated-β-Cyclodextrin as a Chiral Selector in the Mobile Phase

“…Among them, however, only bovine serum albumine protein [11,15] and cellulose tris (3,5-dimethylphenylcarbamate) [16] silica based columns have been employed for ofloxacin enantiomeric separation.…”