Ciprofloxacin decreases plasma phenytoin concentrations in the rat
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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 ratPreview
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References
- 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.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.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.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.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.Davidson D.L.W. (1983): Anticonvulsant drugs. Br. Med. J. Clin. Res., 286, 2043–2045.CrossRefGoogle Scholar
- 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.Dreifus L.S., Watanabe Y. (1970): Current status of diphenylhydantoin. Am. Heart J., 80, 709–713.CrossRefPubMedGoogle Scholar
- 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.Perucca E., Richens A. (1985): Antiepileptic drug interactions. In: Frey N.H., Janz, D. (Eds) Antiepileptic Drugs: Berlin: Springer 833–855.Google Scholar
- 11.Graves N.M. (1993): Pharmacokinetics and interactions of antiepileptic drugs. Am. J. Hosp. Pharm., 50 (suppl 5), S23-S29.PubMedGoogle Scholar
- 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.Gugler R., Aligayer H. (1990): Effects of antacids on the clinical pharmacokinetics of drugs — an update. Clin. Pharmacokinet., 18, 210–219.CrossRefPubMedGoogle Scholar
- 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.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.Marchbanks C.R. (1993): Drug-drug interactions with fluoroquinolones. Pharmacotherapy, 13 (2 Pt2), 23S-28S.PubMedGoogle Scholar
- 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.Hull R.E. (1993): Possible phenytoin-ciprofloxacin interaction (Letter). Ann. Pharmacother., 27, 1283.PubMedGoogle Scholar
- 19.Dillard M.L., Fink R.M., Parkenson R. (1992): Ciprofloxacin-phenytoin interaction (Letter). Ann. Pharmacother., 26, 263.PubMedGoogle Scholar
- 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.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.Perucca E. (1982): Pharmacokinetic interactions with antiepileptic drugs. Clin. Pharmacokinet., 7, 57–84.CrossRefPubMedGoogle Scholar
- 23.Brouwers J.R. (1992): Drug interactions with quinolone antibacterials. Drug Saf., 7, 268–281.CrossRefPubMedGoogle Scholar
- 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.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.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.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.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