| Ketamine HCl (2- (o-chlorophenyl) -2- (methylamino) cyclohexanone HCl) concentrations in whole blood were used to study the pharmacokinetics of i.v., i.m., oral and rectal administrations, at a dose of 25 mg/kg, in normal domestic cats. Cats were also administered ketamine HCl rectally at a dose of 35 mg/kg. Absorption was rapid with the i.m. and rectal routes, while comparatively slow with the oral route. Systemic availability was 51% (SEM 10) for the i.m. dose, 43.5% (SEM 6.1) for the rectal dose and 19% for the oral dose. The first-pass metabolism effect was thought to be responsible for the low oral bioavailability. The first-pass effect, however, had a minimal influence on the metabolism of ketamine HCl administered rectally. The elimination half-life of the drug was statistically similar in the i.v., i.m., oral and rectal groups, at a 95% level of significance (p ;Rate constants of elimination were used to evaluate potential effects of diuretic agents on the elimination of ketamine HCl from the blood of cats. Furosemide, mannitol, and aminophylline did not significantly alter the ketamine HCl elimination rate constants, although the diuretics had a tendency to prolong elimination. This tendency of furosemide was further substantiated by observing the effect of furosemide on glomerular filtration. The rate of sulfanilate elimination, used as an indicator of glomerular filtration, was significantly decreased in the cats that were administered furosemide. Possible mechanisms for the influence of furosemide on the renal excretion of ketamine HCl are discussed.;The extent of plasma protein binding for ketamine HCl and its only metabolite, norketamine, in the cat was determined in pooled plasma using an equilibrium dialysis technique. The mean values for several replicates at various drug concentrations was 37.34% for ketamine HCl and 36.76% for norketamine. A comparison of drug concentrations and percent binding showed the plasma protein binding of ketamine HCl and norketamine to be independent of the drug concentrations found after administration of usual doses. The potential effects of protein binding on the distribution of ketamine HCl are discussed. |
