A model for determining the influence of hepatic uptake of nondepolarizing muscle relaxants in the pig.
Hepatic uptake and distribution of nondepolarizing muscle relaxants in pigs was investigated. A portocaval shunt preparation enabled the determination of the pharmacodynamics of nondepolarizing muscle relaxants both during temporary liver exclusion and intraportal injection in the same animal. To demonstrate the validity of the model in pigs, in a pilot study the influence of hepatic uptake on neuromuscular blockade by pancuronium (n = 3) and its congener Org 6368 (n = 3) was determined. Thereafter, the influence of hepatic uptake on neuromuscular blockade by gallamine (3.4 mg/kg, n = 5), Org 6368 (0.3 mg/kg, n = 5), and vecuronium (0.1 mg/kg, n = 4 and 0.15 mg/kg, n = 5) was studied in pigs anesthetized with pentobarbital. Each pig received one relaxant, which was injected four consecutive times under different conditions. The first injection was into the jugular vein (iv) the second into the portal vein, the third was iv while the liver was excluded for 10 min and the fourth was iv (control). After each injection the onset time, intensity, recovery rate, and total duration of neuromuscular blockade were measured. These variables were compared between the four injections for each relaxant. In the pilot study the influence of hepatic uptake on neuromuscular blockade was similar for pancuronium and Org 6368. For gallamine the onset time, intensity, recovery rate, and duration of action were similar after all four injections. For Org 6368 the variables of neuromuscular blockade were similar after iv and intraportal injection, but exclusion of the liver prolonged the neuromuscular block.(ABSTRACT TRUNCATED AT 250 WORDS)
Motsch
J
J
Department of Experimental Surgery, Universities of Leiden, The Netherlands.
Hennis
P J
PJ
Zimmermann
F A
FA
Agoston
S
S
D000818:Animals; D005703:Gallamine Triethiodide / Q000493:pharmacokinetics / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D003473:Neuromuscular Nondepolarizing Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D010197:Pancuronium / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D010865:Pilot Projects; D013552:Swine; D014673:Vecuronium Bromide / Q000493:pharmacokinetics
D003473:Neuromuscular Nondepolarizing Agents; C011142:Org 6368; D014673:Vecuronium Bromide; D010197:Pancuronium; D005703:Gallamine Triethiodide