Prolongation by bile salts of the duration of action of a steroidal neuromuscular blocking agent.

The influence of bile salts on the duration of action of the steroidal non-depolarizing neuromuscular blocking agent ORG 6368 was investigated in cats. The intravenous administration of ORG 6368 (100 microgram/kg body wt) caused a maximum neuromuscular blockade of 71 +/- 6% with a duration of action of 3.4 +/- 0.1 min. However, intraportal administration of the same dose caused no significant neuromuscular blockade. Following an infusion of dehydrocholate 320 mumol, lasting for 8 min, the magnitude and the duration of action of the neuromuscular blockade produced by ORG 6368 were increased markedly. This effect of the bile salt is possibly a result of inhibition of the hepatic uptake of ORG 6368, thereby retarding its disappearance from the plasma and consequently prolonging the neuromuscular blockade. The neuromuscular blocking effect of intraportally administered gallamine (1 mg/kg body wt) was not influenced significantly by the infusion of dehydrocholate.