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Department of Anesthesiology

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Clinical pharmacology of doxacurium chloride. A new long-acting nondepolarizing muscle relaxant.

TitleClinical pharmacology of doxacurium chloride. A new long-acting nondepolarizing muscle relaxant.
Publication TypeJournal Article
Year of Publication1988
AuthorsBasta SJ, Savarese JJ, Ali HH, Embree PB, Schwartz AF, Rudd GD, Wastila WB
Date Published1988 Oct
KeywordsAdolescent, Adult, Blood Pressure, Chemical Phenomena, Chemistry, Dose-Response Relationship, Drug, Female, Heart Rate, Histamine, Humans, Hydrolysis, Isoquinolines, Male, Middle Aged, Muscle Contraction, Neuromuscular Nondepolarizing Agents, Osmolar Concentration, Pancuronium, Time Factors

Doxacurium chloride (BW A938U) is a bis-quaternary benzylisoquinolinium diester nondepolarizing neuromuscular blocking compound that is minimally hydrolyzed by human plasma cholinesterase. The effect of bolus doses of doxacurium ranging from 10 to 80 micrograms/kg were studied in 81 consenting ASA physical status I and II patients anesthetized with nitrous oxide-oxygen-fentanyl-thiopental. The neuromuscular and cardiovascular effects of doxacurium were compared with those of eight patients receiving 100 micrograms/kg of pancuronium receiving identical anesthesia. The calculated ED95 for evoked twitch inhibition of the adductor pollicis at 0.15 Hz was 30 micrograms/kg. At 1.3 times the ED95 dose of doxacurium, recovery times to 5% and 25% of control twitch height were 59.2 +/- 4.1 (n = 23 of 26) and 75.7 +/- 5.6 (n = 23 of 26) min respectively. For pancuronium comparable recovery times were 81.7 +/- 10.3 (n = 8 of 8) and 83.0 +/- 8.4 (n = 5 of 8) min. Residual doxacurium blockade was readily antagonized by neostigmine. No dose-related effect on heart rate or mean arterial pressure was seen with doxacurium at doses up to and including 2.7 times the ED95 (80 micrograms/kg). Doxacurium administration did not result in any elevation of plasma histamine at doses up to and including 2.7 times the ED95. In this study doxacurium appears to be a long-acting nondepolarizing relaxant with readily reversible neuromuscular blocking effects and devoid of cardiovascular effects. This profile offers clinical advantages over current long-acting agents and further clinical trials seem appropriate.

Alternate JournalAnesthesiology
PubMed ID2972233