Pharmacokinetics of 51W89: preliminary data

Abstract

The pharmacokinetics of the 1R cis‐1'R cis‐isomer of atracurium (51W89) and its metabolite, laudanosine, were studied in 11 healthy patients with normal renal function and in 12 patients with chronic renal failure undergoing regular dialysis. A bolus dose of 51W89 (0.1 mg/kg) was given, and the plasma concentration was measured at regular intervals for 480 min. The elimination half‐life of 51W89 was significantly longer in renal failure patients than in healthy controls (38.9 min vs 30.6 min; P(0.05). The plasma laudanosine levels were lower than those reported after an equipotent dose of atracurium besylate. 51W89 may have a prolonged effect in renal failure patients.

Xylazine Premedication does not Modify the Onset and Duration of Cisatracurium Blockade in Anaesthetized Dogs

“…In theory, these problems are more likely to occur in dogs with kidney or liver disease. Although laudanosine is a metabolite of cisatracurium, the higher potency of this drug compared with atracurium means that lower doses are required which in turn means that plasma metabolite levels be lower (Eastwood et al., 1995; Hunter et al., 1995; Boyd et al., 1996; Kisor et al, 1996). So cisatracurium may prove a useful and safer alternative to atracurium for use in patients with impaired hepatic functions.…”

The use of the nondepolarizing neuromuscular blocking drug cis-atracurium in dogs

“…Although laudanosine is a metabolite of cis‐atracurium, the higher potency of this drug compared with atracurium means that lower doses are required which in turn means that plasma metabolite levels will be lower (Eastwood et al. 1995; Hunter et al 1995; Kisor et al. 1996; Boyd et al.…”

In reply

“…9,10 When cisatracurium is administrated instead of atracurium, plasma laudanosine concentrations are lower. [11][12][13] Although after the administration of cisatracurium plasma concentrations of laudanosine are up to one fifth of that following atracurium, 14 it is generally accepted that laudanosine concentrations are one third of those following an equipotent dose of atracurium. 9 Laudanosine has aroused concern because of possible excitement and seizure activity in the newborn, but the low concentrations observed confirm that the drug can be safely used in caesarean section.…”