Pharmacokinetics of cyclosporine and multiple-dose diclofenac during coadministration

J Clin Pharmacol. 1993 Oct;33(10):936-43. doi: 10.1002/j.1552-4604.1993.tb01926.x.


Pursuant to anecdotal case reports of a possible drug-drug interaction between cyclosporine and diclofenac, an open, two-period crossover study in 24 healthy male volunteers was undertaken in which a single oral dose of 300 mg cyclosporine was administered alone and on day 8 of multiple oral dosing of 50 mg diclofenac every 8 hours. Serial blood samples were obtained over 48 hours after each cyclosporine dose and over a dosing interval for diclofenac on day 7 (diclofenac alone) and day 8 (coadministration of diclofenac with cyclosporine). The mean pharmacokinetic characteristics of cyclosporine were unchanged during coadministration with diclofenac. Based on area under the curve comparison, lack of a pharmacokinetic interaction was conclusively demonstrated for the extent of cyclosporine absorption. The diclofenac maximum plasma concentration and area under the curve over a dosing interval were significantly increased during coadministration; however, a straightforward interpretation of the statistical results was confounded by pronounced variability in diclofenac pharmacokinetics. The results underscore the need for continued caution when cyclosporine and diclofenac are coadministered.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Administration, Oral
  • Adult
  • Cyclosporine / administration & dosage
  • Cyclosporine / blood
  • Cyclosporine / pharmacokinetics*
  • Diclofenac / administration & dosage
  • Diclofenac / blood
  • Diclofenac / pharmacokinetics*
  • Drug Administration Schedule
  • Drug Interactions
  • Humans
  • Male
  • Models, Biological
  • Time Factors


  • Diclofenac
  • Cyclosporine