Cyclosporine can increase isoflurane MAC.
Previous reports indicate that cyclosporine increases sleeping time from barbiturate administration, and analgesia from fentanyl administration, suggesting a possible contribution of cyclosporine to anesthesia. Accordingly, we determined whether cyclosporine pretreatment decreases isoflurane MAC (the minimum alveolar concentration of anesthetic required to eliminate movement in response to noxious stimulation in 50% of subjects) in rats, and whether cyclosporine changes the hindpaw withdrawal latency (HPWL) test to thermal nociceptive stimulation. We assigned rats to receive vehicle (control; n = 18), 7.5 mg. kg(-1). d(-1) cyclosporine (n = 10), or 15 mg. kg(-1). d(-1) cyclosporine (n = 20). MAC was determined before and immediately after 3 days of treatment. HPWL was determined after 3 days of treatment in controls (vehicle) and cyclosporine (15 mg. kg(-1). d(-1)) treated animals. Cyclosporine 7.5 and 15 mg. kg(-1). d(-1) increased MAC by 10.4% +/- 7.3% and 23.1% +/- 17.1% (mean +/- SD) (P < 0.05), respectively. The changes in isoflurane MAC correlated significantly with cyclosporine blood concentrations. Cyclosporine did not significantly increase HPWL. Contrary to our hypotheses, cyclosporine increases rather than decreases MAC, but does not confer appreciable analgesia.


CONCLUSIONS
The immunosuppressive drug, cyclosporine, which is frequently used after organ transplantation, increases the amount of a commonly used anesthetic (isoflurane) necessary to avoid movement to painful stimuli in the rat.
D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007530:Isoflurane / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010147:Pain Measurement / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization
D018686:Anesthetics, Intravenous; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D007530:Isoflurane