Pharmacokinetics, neuromuscular effects, and biodisposition of 3-desacetylvecuronium (Org 7268) in cats.
The pharmacokinetics, biodisposition, and neuromuscular blocking properties of 3-desacetylvecuronium were studied in 17 adult cats. Animals were divided into three groups: five cats with kidney failure induced by bilateral ligation of the renal pedicles, six cats with galactosamine-induced fulminant hepatitis, and six control cats. An intravenous bolus of 300 micrograms.kg-1 of 3-desacetylvecuronium was rapidly injected into the jugular vein. Arterial blood, urine, and bile samples were collected at regular intervals for 6 h in control cats and for 8 h in cats with kidney or liver failure. The liver was excised for analysis at the end of the experiment. In cats with renal failure, 3-desacetylvecuronium pharmacokinetic and pharmacodynamic variables did not differ from those in control cats. In cats with liver failure, plasma clearance was significantly less and mean residence time greater than in control cats (2.8 +/- 0.6 vs. 14.1 +/- 6.5 ml.kg-1.min-1 and 334 +/- 225 vs. 49 +/- 29 min, mean +/- SD, respectively). Volume of distribution at steady state in cats with liver failure and in control cats was not different. Also, in cats with liver failure, the duration of action and recovery index of 3-desacetylvecuronium was significantly greater than in control cats (168 +/- 62 vs. 82 +/- 32 min, and 39 +/- 19 vs. 10 +/- 4 min, respectively). Onset time of neuromuscular blockade was similar in all three groups. Total recovery of 3-desacetylvecuronium, for all three groups, in urine, bile, and liver was 90 +/- 11% (mean +/- SD). In control cats, 70 +/- 18% of 3-desacetylvecuronium was recovered in bile and liver and 19 +/- 14% in urine. No 3,17-bidesacetylvecuronium (a putative 3-desacetylvecuronium metabolite) was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
Segredo
V
V
Department of Anesthesia, University of California San Francisco 94143-0648.
Shin
Y S
YS
Sharma
M L
ML
Gruenke
L D
LD
Caldwell
J E
JE
Khuenl-Brady
K S
KS
Agoston
S
S
Miller
R D
RD
D000818:Animals; D002415:Cats; D056486:Chemical and Drug Induced Liver Injury; D005260:Female; D005688:Galactosamine; D007674:Kidney Diseases / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism; D008297:Male; D009466:Neuromuscular Blocking Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D014018:Tissue Distribution; D014673:Vecuronium Bromide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
D009466:Neuromuscular Blocking Agents; C047940:3-deacetylvecuronium; D005688:Galactosamine; D014673:Vecuronium Bromide