Pharmacokinetics of cyclosporine and multiple-dose diclofenac during coadministration.
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.
Mueller
E A
EA
Department of Human Pharmacology, Sandoz Pharma, Ltd., Basle, Switzerland.
Kovarik
J M
JM
Koelle
E U
EU
Merdjan
H
H
Johnston
A
A
Hitzenberger
G
G
D000284:Administration, Oral; D000328:Adult; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004008:Diclofenac / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D006801:Humans; D008297:Male; D008954:Models, Biological; D013997:Time Factors
D004008:Diclofenac; D016572:Cyclosporine