INTERACTION OF CYCLOSPORIN AND ITS SOLVENT, CREMOPHOR, WITH ATRACURIUM AND VECURONIUM

Interactions between Sandimmun (formulated as cyclosporin (CyA)in Cremophor and ethanol) and atracurium or vecuronium wereinvestigated inanaesthetizedcats. Duringstable50% blockade andwith a constant rate of infusion of the neuromuscular blockingdrugs, Sandimmun 0.8 mg kg^–1 or an equivalent amount ofits solvent moiety was injected over 5 min. Sandimmun potentiatedthe blockade induced by vecuronium (median infusion rate 110µg kg^–1 h^–1) from 50.7% before injection tomaximum 95.2% 17.3 min after injection (median values), whereasthe median blockade in cats receiving atracurium (median 250pig kg^–1 h^–1) increased from 51.3% to 72.4% after32.9 min. At 45 min after the injection the median blockadeswere 93.1% and 69.8%, respectively. In cats receiving vecuronium(median 104 µg kg^–1 h^–1) the solvent producedan increase in effect of from 51.1% to maximum 78.0% blockadeafter 5.4min and 61.5% after 45 min (median values). Interactionwith solvent was negligible in cats receiving atracurium. Weattribute the effect of the solvent to the Cremophor component.The mechanism of the interaction related to the cyclosporinis unknown. ^*Present address: Apothekernes Laboratorium A. S, Harbnitzalleen3, N-0275 Oslo 2, Norway.