Ciprofloxacin decreases plasma phenytoin concentrations in the rat

  • M. S. Al-Humayyd
Article

Summary

The pharmacokinetic interaction between phenytoin and ciprofloxacin was studied in rats. One group of animals was given phenytoin (20 mg/kg, p.o.) as a single daily dose for 7 days. In another group of animals, the same protocol was followed except that ciprofloxacin was given in two equal doses (15 mg/kg, i.p., each) on days 5, 6, and 7. On day 8, phenytoin blood sampling was performed at 0.083, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 10.0 and 12.0 h. Similarly, urine samples were collected at 4, 6, and 8 h following drug administration from the same animals that had received either phenytoin alone or phenytoin together with ciprofloxacin. The concentrations of phenytoin in the plasma and urine were measured using an HPLC method. Ciprofloxacin significantly (P <0.05) reduced the area under the curve (AUC), the maximum plasma concentration (Cmax) and the elimination half-life (t1/2) of phenytoin. Additionally, ciprofloxacin increased phenytoin concentrations in urine at 4, 6, and 8 h. These results show that ciprofloxacin decreases the plasma levels of phenytoin when the two drugs are given concurrently.

Keywords

Ciprofloxacin phenytoin pharmacokinetic interaction rat 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Gleadhill I.C., Ferguson W.P., Lowery R.C. (1986): Efficacy and safety of ciprofloxacin in patients with respiratory infections in comparison with amoxycillin. J. Antimicrob. Chemother., 18 (Suppl. D), 133–138.PubMedGoogle Scholar
  2. 2.
    Scully B.E., Nakatomi M., Ores C., Davidson S., Neu H.C. (1987): Ciprofloxacin therapy in cystic fibrosis. Am. J. Med., 82 (Suppl 4A), 196–201.PubMedGoogle Scholar
  3. 3.
    Schmickler R., Naumann G. (1985): Efficacy of ciprofloxacin in urinary tract infections compared with sulfa-methoxazole/trimethoprim. Leverkusen: Proceedings of the 1st International Ciprofloxacin Workshop, 305–309.Google Scholar
  4. 4.
    Roddy R.E., Handsfield H.H., Hook E.W. (1986): Comparative trial of single-dose ciprofloxacin and ampicillin plus probenecid for treatment of gonococcal urethritis in men. Antimicrob. Agents Chemother., 30, 267–269.PubMedGoogle Scholar
  5. 5.
    Perez-Revalcaba J.A., Quintero-Perez N.P., Morales-Reyes J.J., Huitron-Ramirez J.A., Rodriguez-Chagollan J.J., Rodriguez-Noriega E. (1987): Double-blind comparison of ciprofloxacin with cefotaxime in the treatment of skin and skin structure infections. Am. J. Med., 82 (Suppl. 4A), 242–246.Google Scholar
  6. 6.
    Davidson D.L.W. (1983): Anticonvulsant drugs. Br. Med. J. Clin. Res., 286, 2043–2045.CrossRefGoogle Scholar
  7. 7.
    Zakrzewska J.M., Patsalos P.N. (1992): Drugs used in the management of trigeminal neuralgia. Oral Surg. Oral Med. Oral Pathol., 74, 439–450.CrossRefPubMedGoogle Scholar
  8. 8.
    Dreifus L.S., Watanabe Y. (1970): Current status of diphenylhydantoin. Am. Heart J., 80, 709–713.CrossRefPubMedGoogle Scholar
  9. 9.
    Craig C.R. (1994): Anticonvulsant drugs. In: Craig C.R., Stitzel R.E. (Eds) Modern Pharmacology, 4th edn. London: Little Brown and Company, 413–424.Google Scholar
  10. 10.
    Perucca E., Richens A. (1985): Antiepileptic drug interactions. In: Frey N.H., Janz, D. (Eds) Antiepileptic Drugs: Berlin: Springer 833–855.Google Scholar
  11. 11.
    Graves N.M. (1993): Pharmacokinetics and interactions of antiepileptic drugs. Am. J. Hosp. Pharm., 50 (suppl 5), S23-S29.PubMedGoogle Scholar
  12. 12.
    Van-Slooten A.D., Nix D.E., Wilton J.H., Love J.H., Spivey J.M., Goldstein H.R. (1991): Combined use of ciprofloxacin and sucralfate. DICP, 25, 578–582.PubMedGoogle Scholar
  13. 13.
    Gugler R., Aligayer H. (1990): Effects of antacids on the clinical pharmacokinetics of drugs — an update. Clin. Pharmacokinet., 18, 210–219.CrossRefPubMedGoogle Scholar
  14. 14.
    Jolson H.M., Tanner L.A., Green L., Grasela Jr T.H. (1992): Adverse reaction reporting of interaction between warfarin and fluoroquinolones. Arch. Intern. Med., 152, 1533–1540.CrossRefGoogle Scholar
  15. 15.
    Fuhr U., Wolff T., Harder S., Schymanski P., Staib A.H. (1990): Quinolone inhibition of cytochrome P-450-dependent caffeine metabolism in human liver microsomes. Drug Metab. Dispos., 18, 1005–1010.PubMedGoogle Scholar
  16. 16.
    Marchbanks C.R. (1993): Drug-drug interactions with fluoroquinolones. Pharmacotherapy, 13 (2 Pt2), 23S-28S.PubMedGoogle Scholar
  17. 17.
    Schroeder D., Frye J., Alldredge B., Messing R., Flaherty J. (1990): Effect of ciprofloxacin on serum phenytoin in epileptic patients. Pharmacotherapy, 11, 275.Google Scholar
  18. 18.
    Hull R.E. (1993): Possible phenytoin-ciprofloxacin interaction (Letter). Ann. Pharmacother., 27, 1283.PubMedGoogle Scholar
  19. 19.
    Dillard M.L., Fink R.M., Parkenson R. (1992): Ciprofloxacin-phenytoin interaction (Letter). Ann. Pharmacother., 26, 263.PubMedGoogle Scholar
  20. 20.
    Job M.L., Arn S.K., Strom J.G., Jacobs N.F., D’Souza M.J. (1994): Effect of ciprofloxacin on the pharmacokinetics of multiple-dose phenytoin serum concentrations. Ther. Drug Monit., 16, 427–431.CrossRefPubMedGoogle Scholar
  21. 21.
    Asberg A., Haffner F. (1987): Analysis of serum concentration of phenobarbital, phenytoin, carbamazepine and carbamazepine 10,11-epoxide by solvent recycled liquid chromatography. Scan. J. Clin. Lab. Invest. 47, 389–390.Google Scholar
  22. 22.
    Perucca E. (1982): Pharmacokinetic interactions with antiepileptic drugs. Clin. Pharmacokinet., 7, 57–84.CrossRefPubMedGoogle Scholar
  23. 23.
    Brouwers J.R. (1992): Drug interactions with quinolone antibacterials. Drug Saf., 7, 268–281.CrossRefPubMedGoogle Scholar
  24. 24.
    Lebel M., Bergeron M.G. (1987): Pharmacokinetics in the elderly: studies on ciprofloxacin. Am. J. Med., 82 (Suppl. 4A), 108–114.PubMedGoogle Scholar
  25. 25.
    Toon S., Hopkins K.J., Garstang, F.M., Aarons L., Sedman A., Rowland M. (1987): Enoxacin-warfarin interaction: pharmacokinetic and stereo-chemical aspects. Clin. Pharmacol. Ther., 42, 33–41.PubMedGoogle Scholar
  26. 26.
    Kronbach T., Fischer V., Meyer U.A. (1988): Cyclosporine metabolism in human liver: identification of cytochrome P-450 III gene family as the major cyclosporine-metabolizing enzyme explains interactions of cyclosporine with other drugs. Clin. Pharmacol. Ther., 43, 630–635.PubMedGoogle Scholar
  27. 27.
    Tan K.K.C., Trull A.K., Shawket S. (1989): Co-administration of ciprofloxacin and cyclosporine: lack of evidence for a pharmacokinetic interaction. Br. J. Clin. Pharmacol., 28, 185–187.PubMedGoogle Scholar
  28. 28.
    Arcieri G., Griffith E., Gruenwaldt G. (et al.) (1988): A survey of clinical experience with ciprofloxacin, a new quinolone antimicrobial. J. Clin. Pharmacol., 28, 179–189.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • M. S. Al-Humayyd
    • 1
  1. 1.Department of Medical Pharmacology, College of MedicineKing Saud UniversityRiyadhSaudi Arabia

Personalised recommendations