Interaction of cyclosporin and its solvent, Cremophor, with atracurium and vecuronium. Studies in the cat.

Interactions between Sandimmun (formulated as cyclosporin (CyA) in Cremophor and ethanol) and atracurium or vecuronium were investigated in anaesthetized cats. During stable 50% blockade and with a constant rate of infusion of the neuromuscular blocking drugs, Sandimmun 0.8 mg kg-1 or an equivalent amount of its solvent moiety was injected over 5 min. Sandimmun potentiated the blockade induced by vecuronium (median infusion rate 110 micrograms kg-1 h-1) from 50.7% before injection to maximum 95.2% 17.3 min after injection (median values), whereas the median blockade in cats receiving atracurium (median 250 micrograms kg-1 h-1) increased from 51.3% to 72.4% after 32.9 min. At 45 min after the injection the median blockades were 93.1% and 69.8%, respectively. In cats receiving vecuronium (median 104 micrograms kg-1 h-1) the solvent produced an increase in effect of from 51.1% to maximum 78.0% blockade after 5.4 min and 61.5% after 45 min (median values). Interaction with solvent was negligible in cats receiving atracurium. We attribute the effect of the solvent to the Cremophor component. The mechanism of the interaction related to the cyclosporin is unknown.