Search

The clinical, cardiovascular and respiratory effects after i.v. administration of R8110, a fluoro analogue of etomidate (Fig. 1), were studied in pre-medicated dogs. The clinical observations were made at doses of 3 and 4 mg/kg body weight (BW) injected slowly i.v., whereas cardiovascular and respiratory studies were carried out at a dose rate of 3 mg/kg R8110 i.v. Induction and recovery were smooth and no significant side-effects were observed. The cardiovascular system was slightly influenced, but respiration was hardly affected. The effect of pre-medication on respiration and the cardiovascular system was hardly potentiated by R8110. Although there were significant changes in cardiovascular and biochemical parameters, all values remained within physiological limits. R8110 appeared to be a safe and reliable induction agent.

R 8110, an imidazole derivative, was shown to be clinically superior to etomidate for induction and maintenance of anaesthesia in dogs. The present study compared the effects of intravenous (i.v.) R 8110, etomidate and Ringer solution on cortisol biosynthesis by the adrenal gland in seven male labradors. A tetracosactide challenge was carried out 30 min after the i.v. injection of 3 mg/kg of both drugs and after i.v. Ringer solution (1 ml/kg). Etomidate and R 8110 both suppressed the cortisol response to tetracosactide almost completely and increased the plasma 11 beta-deoxycortisol levels more than 20 fold. Maximal 11 beta-deoxycortisol values were reached 120 min after R 8110, and not less than 300 min after etomidate. Plasma 17 alpha-hydroxyprogesterone and testosterone concentrations did not differ between placebo and R 8110 treatment, but they decreased after etomidate. These results indicate that the effects of R 8110 on steroid biosynthesis in dogs are less pronounced than those of etomidate and are largely limited to a temporary inhibition of the 11 beta-hydroxylase in the adrenal gland.

The pharmacokinetics and clinical effects of the short-acting hypnotic R 8110 and of the narcotic analgesic fentanyl were studied in the dog. The effects of separate intravenous (i.v.) injections of R 8110 (4 mg/kg) and fentanyl (0.015 mg/kg) and of concurrent i.v. injection of the two were studied. After administration of R 8110, induction of hypnosis occurred within 1 min, maximal depth of anaesthesia and satisfactory analgesia and muscle relaxation were obtained after 5 min. The effects had decreased within 15 min and full recovery occurred within 30 min. Fentanyl alone produced neither hypnosis nor muscle relaxation. When fentanyl and R 8110 were given simultaneously, the duration of hypnosis was doubled in comparison with R 8110 alone. Moreover, markedly improved and longer lasting analgesia and muscle relaxation were observed with the combination. When the drugs were injected together, the plasma concentrations of R 8110 were initially much higher than after separate injection of R 8110, but they became similar after 30 min. Although statistically non-significant, fentanyl reduced the total plasma clearance of R 8110 (31.1 +/- 6.9 vs. 21.9 +/- 2.3 ml/kg/min) and decreased the volume of distribution (3.78 +/- 1.83 vs. 2.23 +/- 0.90 l/kg, P less than 0.05). Fentanyl did not alter the elimination half-life of R 8110. R 8110 had no apparent influence on the pharmacokinetics of fentanyl.

R 51163, a purine alkyl piperidine derivative, has been shown to produce reliable sedation in cattle of varying age and breed in three different types of experiments: transport and regrouping of cattle which had only been handled occasionally; manipulations and minor interventions; minor and major surgery with or without supplementary local anaesthesia. With dose rates of R 51163 at 0.05 mg/kg i.v. and of 0.10-0.15 mg/kg i.m. sedation became prominent within 10-15 min and lasted at least 60 min. Caesarean sections were performed under adequate sedation with R 51163 with dose ranging from 0.018 to 0.05 mg/kg i.v. and from 0.075 to 0.10 mg/kg i.m. The data suggest possible increased responsiveness to the drug at the time of calving.