Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1997 Oct;41(10):2274–2277. doi: 10.1128/aac.41.10.2274

Absorption of ofloxacin isomers in the rat small intestine.

L Rabbaa 1, S Dautrey 1, N Colas-Linhart 1, C Carbon 1, R Farinotti 1
PMCID: PMC164106  PMID: 9333061

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.

Full Text

The Full Text of this article is available as a PDF (156.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amidon G. L., Lee H. J. Absorption of peptide and peptidomimetic drugs. Annu Rev Pharmacol Toxicol. 1994;34:321–341. doi: 10.1146/annurev.pa.34.040194.001541. [DOI] [PubMed] [Google Scholar]
  2. Barr W. H., Riegelman S. Intestinal drug absorption and metabolism. I. Comparison of methods and models to study physiological factors of in vitro and in vivo intestinal absorption. J Pharm Sci. 1970 Feb;59(2):154–163. doi: 10.1002/jps.2600590204. [DOI] [PubMed] [Google Scholar]
  3. Barre J., Houin G., Tillement J. P. Dose-dependent pharmacokinetic study of pefloxacin, a new antibacterial agent, in humans. J Pharm Sci. 1984 Oct;73(10):1379–1382. doi: 10.1002/jps.2600731014. [DOI] [PubMed] [Google Scholar]
  4. Bressolle F., Gonçalves F., Gouby A., Galtier M. Pefloxacin clinical pharmacokinetics. Clin Pharmacokinet. 1994 Dec;27(6):418–446. doi: 10.2165/00003088-199427060-00003. [DOI] [PubMed] [Google Scholar]
  5. Fujimoto T., Mitsuhashi S. In vitro antibacterial activity of DR-3355, the S-(-)-isomer of ofloxacin. Chemotherapy. 1990;36(4):268–276. doi: 10.1159/000238777. [DOI] [PubMed] [Google Scholar]
  6. Furet Y. X., Deshusses J., Pechère J. C. Transport of pefloxacin across the bacterial cytoplasmic membrane in quinolone-susceptible Staphylococcus aureus. Antimicrob Agents Chemother. 1992 Nov;36(11):2506–2511. doi: 10.1128/aac.36.11.2506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Griffiths N. M., Hirst B. H., Simmons N. L. Active intestinal secretion of the fluoroquinolone antibacterials ciprofloxacin, norfloxacin and pefloxacin; a common secretory pathway? J Pharmacol Exp Ther. 1994 May;269(2):496–502. [PubMed] [Google Scholar]
  8. Griffiths N. M., Hirst B. H., Simmons N. L. Active secretion of the fluoroquinolone ciprofloxacin by human intestinal epithelial Caco-2 cell layers. Br J Pharmacol. 1993 Mar;108(3):575–576. doi: 10.1111/j.1476-5381.1993.tb12844.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Harder S., Fuhr U., Beermann D., Staib A. H. Ciprofloxacin absorption in different regions of the human gastrointestinal tract. Investigations with the hf-capsule. Br J Clin Pharmacol. 1990 Jul;30(1):35–39. doi: 10.1111/j.1365-2125.1990.tb03740.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hayakawa I., Atarashi S., Yokohama S., Imamura M., Sakano K., Furukawa M. Synthesis and antibacterial activities of optically active ofloxacin. Antimicrob Agents Chemother. 1986 Jan;29(1):163–164. doi: 10.1128/aac.29.1.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hirano T., Iseki K., Miyazaki S., Takada M., Kobayashi M., Sugawara M., Miyazaki K. The stimulative effect of diffusion potential on enoxacin uptake across rat intestinal brush-border membranes. J Pharm Pharmacol. 1994 Aug;46(8):676–679. doi: 10.1111/j.2042-7158.1994.tb03881.x. [DOI] [PubMed] [Google Scholar]
  12. Iseki K., Hirano T., Fukushi Y., Kitamura Y., Miyazaki S., Takada M., Sugawara M., Saitoh H., Miyazaki K. The pH dependent uptake of enoxacin by rat intestinal brush-border membrane vesicles. J Pharm Pharmacol. 1992 Sep;44(9):722–726. doi: 10.1111/j.2042-7158.1992.tb05507.x. [DOI] [PubMed] [Google Scholar]
  13. Korten V., Murray B. E. Impact of the fluoroquinolones on gastrointestinal flora. Drugs. 1993;45 (Suppl 3):125–133. doi: 10.2165/00003495-199300453-00021. [DOI] [PubMed] [Google Scholar]
  14. Le Coguic A., Bidault R., Farinotti R., Dauphin A. Determination of ofloxacin in plasma and urine by liquid chromatography. J Chromatogr. 1988 Dec 29;434(1):320–323. doi: 10.1016/0378-4347(88)80095-1. [DOI] [PubMed] [Google Scholar]
  15. Okazaki O., Kojima C., Hakusui H., Nakashima M. Enantioselective disposition of ofloxacin in humans. Antimicrob Agents Chemother. 1991 Oct;35(10):2106–2109. doi: 10.1128/aac.35.10.2106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Okazaki O., Kurata T., Tachizawa H. Stereoselective metabolic disposition of enantiomers of ofloxacin in rats. Xenobiotica. 1989 Apr;19(4):419–429. doi: 10.3109/00498258909042283. [DOI] [PubMed] [Google Scholar]
  17. Pascual A., Garcia I., Perea E. J. Fluorometric measurement of ofloxacin uptake by human polymorphonuclear leukocytes. Antimicrob Agents Chemother. 1989 May;33(5):653–656. doi: 10.1128/aac.33.5.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ponz F., Ilundain A., Lluch M. Method for successive absorptions with intestinal perfusion in vivo. Rev Esp Fisiol. 1979 Mar;35(1):97–103. [PubMed] [Google Scholar]
  19. Prieto J. G., Barrio J. P., Alvarez A. I., Gómez G. Kinetic mechanism for the intestinal absorption of ofloxacin. J Pharm Pharmacol. 1988 Mar;40(3):211–212. doi: 10.1111/j.2042-7158.1988.tb05223.x. [DOI] [PubMed] [Google Scholar]
  20. SCHANKER L. S., TOCCO D. J., BRODIE B. B., HOGBEN C. A. Absorption of drugs from the rat small intestine. J Pharmacol Exp Ther. 1958 May;123(1):81–88. [PubMed] [Google Scholar]
  21. Savina P. M., Staubus A. E., Gaginella T. S., Smith D. F. Optimal perfusion rate determined for in situ intestinal absorption studies in rats. J Pharm Sci. 1981 Mar;70(3):239–243. doi: 10.1002/jps.2600700303. [DOI] [PubMed] [Google Scholar]
  22. Stuck A. E., Kim D. K., Frey F. J. Fleroxacin clinical pharmacokinetics. Clin Pharmacokinet. 1992 Feb;22(2):116–131. doi: 10.2165/00003088-199222020-00003. [DOI] [PubMed] [Google Scholar]
  23. Tanaka M., Kurata T., Fujisawa C., Ohshima Y., Aoki H., Okazaki O., Hakusui H. Mechanistic study of inhibition of levofloxacin absorption by aluminum hydroxide. Antimicrob Agents Chemother. 1993 Oct;37(10):2173–2178. doi: 10.1128/aac.37.10.2173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tsuji A., Miyamoto E., Kagami I., Sakaguchi H., Yamana T. GI absorption of beta-lactam antibiotics I: kinetic assessment of competing absorption and degradation in GI tract. J Pharm Sci. 1978 Dec;67(12):1701–1704. doi: 10.1002/jps.2600671218. [DOI] [PubMed] [Google Scholar]
  25. Tsuji A., Nakashima E., Kagami I., Yamana T. Intestinal absorption mechanism of amphoteric beta-lactam antibiotics I: Comparative absorption and evidence for saturable transport of amino-beta-lactam antibiotics by in situ rat small intestine. J Pharm Sci. 1981 Jul;70(7):768–772. doi: 10.1002/jps.2600700714. [DOI] [PubMed] [Google Scholar]
  26. Westphal J. F., Jehl F., Brogard J. M., Carbon C. Amoxicillin intestinal absorption reduction by amiloride: possible role of the Na(+) -H+ exchanger. Clin Pharmacol Ther. 1995 Mar;57(3):257–264. doi: 10.1016/0009-9236(95)90150-7. [DOI] [PubMed] [Google Scholar]
  27. Wise R., Lister D., McNulty C. A., Griggs D., Andrews J. M. The comparative pharmacokinetics of five quinolones. J Antimicrob Chemother. 1986 Nov;18 (Suppl 500):71–81. doi: 10.1093/jac/18.supplement_d.71. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES