Hypnoanalgesia with R 8110/fentanyl in the dog: pharmacodynamic and pharmacokinetic interactions.
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.
Monbaliu
J
J
Department of Drug Metabolism and Pharmacokinetics, Janssen Pharmaceutica, Beerse, Belgium.
Degryse
A D
AD
Ooms
L A
LA
Van Dijk
P
P
Lagerweij
E
E
Michiels
M
M
Woestenborghs
R
R
Heykants
J
J
D000818:Animals; D004285:Dogs / Q000502:physiology*; D005045:Etomidate / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D005283:Fentanyl / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male
D006993:Hypnotics and Sedatives; C052803:R 8110; D005283:Fentanyl; D005045:Etomidate