Clinical pharmacology of doxacurium chloride. A new long-acting nondepolarizing muscle relaxant.
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.
Basta
S J
SJ
Department of Anaesthesia, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
Savarese
J J
JJ
Ali
H H
HH
Embree
P B
PB
Schwartz
A F
AF
Rudd
G D
GD
Wastila
W B
WB
D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000097:blood; D006801:Humans; D006868:Hydrolysis; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology; D009994:Osmolar Concentration; D010197:Pancuronium / Q000494:pharmacology; D013997:Time Factors
D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D006632:Histamine; D010197:Pancuronium; C049429:doxacurium