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J Thorac Cardiovasc Surg 1994;107:1365-1366
© 1994 Mosby, Inc.

LETTERS TO THE EDITOR

Invited letter concerning: Acute interstitial nephritis in a cardiac transplant recipient receiving ciprofloxacin

Luis J. Rosado, MD, Mark S. Siskind, MD, Paul E. Nolan, PharmD, Jack G. Copeland, MD

University of Arizona Heart Center
1501 N. Campbell Ave.
Tucson, AZ 85724

Reply to the Editor:

We thank Dr. Bourge for his comments regarding our report describing the occurrence of acute interstitial nephritis in a cardiac transplant recipient receiving ciprofloxacin, a fluoroquinolone antibiotic. We agree that the mechanism of the acute interstitial nephritis is not likely due to a pharmacokinetic interaction between ciprofloxacin and cyclosporine. Ciprofloxacin does not appear to alter the pharmacokinetics of cyclosporine in healthy human volunteers,Go 1 renal transplant recipients,Go 2 or bone marrow transplant recipients.Go 3 Furthermore, no significant changes in cyclosporine serum concentrations were noted in orthotopic heart transplant recipients who were coadministered ciprofloxacin.Go 4 Cyclosporine is hepatically metabolized by an isozyme of cytochrome P450, namely CYP3A4.Go 5 Fluoroquinolones have no significant inhibitory effects on this isozyme.Go 6 In addition, cyclosporine would not appear to significantly alter the pharmacokinetics of ciprofloxacinGo Go 1,3

It remains difficult to determine whether the combination of cyclosporine and ciprofloxacin act "synergistically" to produce interstitial nephritis. In a review of 146 clinical trials with oral ciprofloxacin that incorporated 2829 patient records, Arcieri and associatesGo 7 reported only one instance of acute interstitial nephritis. In addition, they reported single occurrences each of acute renal failure and nonspecific nephritis. Thus the incidence of ciprofloxacin-induced acute interstitial nephritis is low in patients not receiving transplants.

The prevalence of acute interstitial nephritis resulting from ciprofloxacin in transplant recipients receiving cyclosporine is unknown. Nonetheless, we reiterate our recommendation to closely monitor the renal function of heart transplant patients who are prescribed ciprofloxacin.

References

  1. Tan KKC, Trull AK, Shawket S. Co-administration of ciprofloxacin and cyclosporine: lack of evidence for a pharmacokinetic interaction. Br J Clin Pharmacol 1989;28:185-17.[Medline]
  2. Van Buren DH, Koestner J, Adedoyin A, et al. Effect of ciprofloxacin on cyclosporine pharmacokinetics. Transplantation 1990;50:888-9.[Medline]
  3. Kruger HU, Shuler U, Proksch B, Gobel M, Ehninger G. Investigation of potential interaction of ciprofloxacin with cyclosporine in bone marrow transplant recipients. Antimicrob Agents Chemother 1990;34:1048-52.[Abstract/Free Full Text]
  4. Robinson JA, Venezio FR, Costanzo-Nordin MR, Pifarré R, O'Keefe PJ. Patients receiving quinolones and cyclosporine after heart transplantation. J Heart Transplant 1990;9:30-1.[Medline]
  5. Kronback T, Fischer V, Meyer UA. Cyclosporine metabolism in human liver: identification of a cytochrome P-450III gene family as the major cyclosporine-metabolizing enzyme explains interactions of cyclosporine with other drugs. Clin Pharmacol Ther 1988;43:630-5.[Medline]
  6. Sarkar M, Polk RE, Guzelian PS, Hunt C, Karnes HT. In vitro effect of fluoroquinolones on theophylline metabolism in human liver microsomes. Antimicrob Agents Chemother 1990;34:594-9.[Abstract/Free Full Text]
  7. Arcieri G, Griffith E, Gruenwaldt G, et al. Ciprofloxacin: an update on clinical experience. Am J Med 1987;82(Suppl 4A):381-6.[Medline]




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