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Pharmacokinetics of Cyclosporine and Multiple‐Dose Diclofenac During Coadministration
Author(s) -
Mueller Edgar A.,
Kovarik John M.,
Koelle Ernst U.,
Merdjan Henri,
Johnston Atholl,
Hitzenberger Gerhart
Publication year - 1993
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1993.tb01926.x
Subject(s) - diclofenac , pharmacokinetics , dosing , pharmacology , medicine , drug interaction , crossover study , oral administration , alternative medicine , pathology , placebo
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.