Influence of general anaesthesia on the intravenous acetaminophen pharmacokinetics in Beagle dogs.

OBJECTIVE: To determine if general anaesthesia influences the intravenous (IV) pharmacokinetics (PK) of acetaminophen in dogs. STUDY DESIGN: Prospective, crossover, randomized experimental study. ANIMALS: A group of nine healthy Beagle dogs. METHODS: Acetaminophen PK were determined in conscious and anaesthetized dogs on two separate occasions. Blood samples were collected before, and at 5, 10, 15, 30, 45, 60 and 90 minutes and 2, 3, 4, 6, 8, 12 and 24 hours after 20 mg kg-1 IV acetaminophen administration. Haematocrit, total proteins, albumin, alanine aminotransferase, aspartate aminotransferase, urea and creatinine were determined at baseline and 24 hours after acetaminophen. The anaesthetized group underwent general anaesthesia (90 minutes) for dental cleaning. After the administration of dexmedetomidine (3 µg kg-1) intramuscularly, anaesthesia was induced with propofol (2-3 mg kg-1) IV, followed by acetaminophen administration. Anaesthesia was maintained with isoflurane in 50% oxygen (Fe'Iso 1.3-1.5%). Dogs were mechanically ventilated. Plasma concentrations were analysed with high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling. A Wilcoxon test was used to compare PK data between groups, and clinical laboratory values between groups, and before versus 24 hours after acetaminophen administration. Data are presented as median and range (p < 0.05). RESULTS: A two-compartmental model best described time-concentration profiles of acetaminophen. No significant differences were found for volume of distribution values 1.41 (0.94-3.65) and 1.72 (0.89-2.60) L kg-1, clearance values 1.52 (0.71-2.30) and 1.60 (0.91-1.78) L kg-1 hour-1 or terminal elimination half-life values 2.45 (1.45-8.71) and 3.57 (1.96-6.35) hours between conscious and anaesthetized dogs, respectively. Clinical laboratory variables were within normal range. No adverse effects were recorded. CONCLUSIONS AND CLINICAL RELEVANCE: IV acetaminophen PK in healthy Beagle dogs were unaffected by general anaesthesia under the study conditions. Further studies are necessary to evaluate the PK in different clinical contexts.

Pharmacokinetics of the individual enantiomer S-(+)-ketoprofen after intravenous and oral administration in dogs at two dose levels.

The pharmacokinetic of the individual S-(+)-enantiomer of ketoprofen, S-(+)-ketoprofen, after intravenous (IV) and oral (PO) administration was determined in six dogs at 1 and 3 mg/kg. Plasma concentrations were determined by high performance liquid chromatography with ultraviolet detection. The concentration-time curves were analyzed by non-compartmental methods. Steady-state volume of distribution (Vss) and clearance (Cl) of S-(+)-ketoprofen after IV administration were 0.22 ± 0.07 and 0.19 ± 0.03 L/kg, and 0.10 ± 0.02 and 0.09 ± 0.01 L/h/kg, at 1 and 3 mg/kg, respectively. Following PO administration, S-(+)-ketoprofen achieved maximum plasma concentrations of 4.91 ± 0.76 and 12.47 ± 0.62 µg/ml, at two dose levels, respectively. The absolute bioavailability after PO route was 88.66 ± 12.95% and 85.36 ± 13.90%, respectively.

Cardiorespiratory and anaesthetic effects of two continuous rate infusions of dexmedetomidine in alfaxalone anaesthetized dogs.

Six Beagles were used in this prospective randomised crossover experimental study. Dexmedetomidine was administered at 0, 1 or 2 µg/kg IV for group C, LDA and HDA, respectively. Animals were induced and maintained with alfaxalone at 0.07 mg/kg/min with a CRI dexmedetomidine dose of 0, 0.5 or 1 µg/kg/h for group C, LDA and HDA, respectively. Cardiorespiratory variables, arterial blood gases and depth of anaesthesia were recorded. The recovery times and quality of recovery were scored. Group HDA produced a greater increase in the depth of anaesthesia than LDA. However, with both protocols, CI was halved compared to normal values in dogs. The use of oxygen before and during the anaesthetic maintenance is advisable, mainly if dexmedetomidine is going to be use as a pre-medicant and maintenance agent. The quality of recovery was better in groups receiving dexmedetomidine, without causing an increase in recovery time.

Cardiorespiratory, anaesthetic and recovery effects of morphine combined with medetomidine and alfaxalone in rabbits.

Ten New Zealand White rabbits were used in a crossover experimental study: 200 µg/kg medetomidine and 1 (M1) or 2 mg/kg (M2) morphine were administered intramuscularly. After preoxygenation, anaesthesia was induced with alfaxalone at 10 mg/kg intravenously. The trachea was intubated and 60 per cent oxygen provided. Heart and respiratory rates (HR and RR), direct arterial pressures (APs), arterial pH (pHa), PaO2, PaCO2 and SaO2 were taken at baseline, after premedication and every 10 minutes during the 90 minutes following induction. The times to return the ear pinch, toe pinch and righting reflexes were recorded. Data were analysed using a two-way analysis of variance and a paired samples t test. Compared to baseline values, HR, RR, APs, PaO2 and SaO2 decreased significantly after premedication in both groups. Postinduction apnoea of 20 ± 10 with M1 and 27 ± 18 minutes with M2 was experienced following alfaxalone administration, intermitent positive pressure ventilation was applied until spontaneous breathing efforts appeared. Cardiovascular variables, RR and pHa remained below, and PaCO2 over baseline values during the anaesthetic period. No significant differences were observed in the recovery times. Morphine at 1 or 2 mg/kg combined with medetomidine and alfaxalone in rabbits produced a suitable level of anaesthesia, although profound cardiorespiratory depression was found.