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

Anesthesiology. 1988 Oct;69(4):478-86. doi: 10.1097/00000542-198810000-00006.

Abstract

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blood Pressure / drug effects
  • Chemical Phenomena
  • Chemistry
  • Dose-Response Relationship, Drug
  • Female
  • Heart Rate / drug effects
  • Histamine / blood
  • Humans
  • Hydrolysis
  • Isoquinolines / pharmacology*
  • Male
  • Middle Aged
  • Muscle Contraction / drug effects
  • Neuromuscular Nondepolarizing Agents / pharmacology
  • Osmolar Concentration
  • Pancuronium / pharmacology
  • Time Factors

Substances

  • Isoquinolines
  • Neuromuscular Nondepolarizing Agents
  • Histamine
  • Pancuronium
  • doxacurium