Henning A Haga

Pharmacokinetics and pharmacodynamics of meloxicam in piglets

The pharmacokinetics and pharmacodynamics of meloxicam in piglets (16-23 days old) were studied using a stratified parallel group design. One group (n = 13) received 0.4 mg/kg meloxicam intravenously, while the other group (n = 12) received physiological saline solution. A carrageenan-sponge model of acute inflammation was used to evaluate the effects of meloxicam. The plasma clearance was low (0.061 L/kg/h), the volume of distribution was low (0.19 L/kg) and the elimination half-life was short (2.7 h). At most time points, the mean concentration of meloxicam in plasma exceeded the concentrations in exudate indicating a limited accumulation of the drug at the site of the inflammation. There were significant differences between the groups in the exudate prostaglandin E2 (PGE2) concentration, but the inhibition of PGE2 in the meloxicam group was limited. The inhibition of thromboxane B(2) (TXB2) production in serum in the meloxicam group was extensive, but of shorter duration than the PGE2 inhibition in exudate.

Ketoprofen in piglets: enantioselective pharmacokinetics, pharmacodynamics and PK/PD modelling.

The chiral pharmacokinetics and pharmacodynamics of ketoprofen were investigated in a placebo-controlled study in piglets after intramuscular administration of 6 mg/kg racemic ketoprofen. The absorption half-lives of both enantiomers were short, and S-ketoprofen predominated over R-ketoprofen in plasma. A kaolin-induced inflammation model was used to evaluate the anti-inflammatory, antipyretic and analgesic effects of ketoprofen. Skin temperatures increased after the kaolin injection, but the effect of ketoprofen was small. No significant antipyretic effects could be detected, but body temperatures tended to be lower in the ketoprofen-treated piglets. Mechanical nociceptive threshold testing was used to evaluate the analgesic effects. The piglets in the ketoprofen-treated group had significantly higher mechanical nociceptive thresholds compared to the piglets in the placebo group for 12-24 h following the treatment. Pharmacokinetic/pharmacodynamic modelling of the results from the mechanical nociceptive threshold testing gave a median IC(50) for S-ketoprofen of 26.7 μg/mL and an IC(50) for R-ketoprofen of 1.6 μg/mL. This indicates that R-ketoprofen is a more potent analgesic than S-ketoprofen in piglets. Estimated ED(50) for racemic ketoprofen was 2.5 mg/kg.

Pharmacokinetics and pharmacodynamic effects of meloxicam in piglets subjected to a kaolin inflammation model

The pharmacokinetics and the analgesic, anti-inflammatory and antipyretic effects of meloxicam were investigated in a placebo controlled study in 2-week-old piglets. Inflammation was induced by a subcutaneous injection of kaolin in the left metacarpus, and 16 h later, meloxicam (0.6 mg/kg) or saline was administered intramuscularly. The absorption half-life was relatively short (0.19 h) and the elimination half-life was 2.6 h. Mechanical nociceptive threshold testing was used to evaluate the analgesic effect, but no significant effect of the meloxicam treatment was found. The skin temperature of the inflamed area increased after the kaolin injection, but no significant decrease in temperature was found after administration of meloxicam. Only limited pyresis was observed after the kaolin injection, and no significant antipyretic effect of meloxicam was found. The results indicated that this dose of meloxicam had very limited anti-inflammatory and analgesic effects in piglets.

Field anaesthetic and surgical techniques for implantation of intraperitoneal radio transmitters in Eurasian beavers Castor fiber

Radio transmitters were implanted intraperitoneally in 22 (nine females, 13 males) adult, territorial Eurasian beavers Castor fiber under field conditions. Two different injectable anaesthestic drug combinations were tested. Access to the peritoneal cavity was made through a ventral midline incision. The animals in group # 1 (N = 10) were initially injected with medetomidine (0.05 mg/kg), ketamine (5 mg/kg) and butorphanol (0.1 mg/kg). Three animals needed additional injections of the drug combination. Muscle relaxation was poor and variable and some of the animals were sound sensitive. When midazolam (0.25 mg/kg) was added to the drug combination (group # 2), muscle relaxation was excellent and the beavers (N = 12) did not react to sound stimuli. All surgeries were successfully performed. One animal in group # 1 died postoperatively due to circulatory failure. The behaviour and movements of the beavers did not appear to be affected by the procedure or the implant, except for the first few days when more time was spent inside the lodges. All beavers stayed in their original territory until they died, or as long as 17–24 months after the implantation. Based on these results, it appears that an injectable drug combination based on medetomidine, ketamine, butorphanol and midazolam and a surgical access through the ventral midline is suitable for implanting radio transmitters intraperitoneally in beavers under field conditions.

Gastrointestinal stromal tumour and hypoglycemia in a Fjord pony: case report.

BackgroundNeoplasia may cause hypoglycemia in different species including the horse, but hypoglycemia has not previously been reported in the horse associated with gastrointestinal stromal tumours.Case presentationA case of a gastrointestinal stromal tumour in a Fjord pony with severe recurrent hypoglycemia is presented. The mechanism causing the hypoglycemia was not established.ConclusionThis case indicates that a gastrointestinal stromal tumour may cause hypoglycemia also in the horse.

Antinociceptive effects of three escalating dexmedetomidine and lignocaine constant rate infusions in conscious horses.

Dexmedetomidine and lignocaine IV are used clinically to provide analgesia in horses. The aims of this study were to investigate the antinociceptive effects, plasma concentrations and sedative effects of 2, 4 and 6 µg/kg/h dexmedetomidine IV, with a bolus of 0.96 µg/kg preceding each continuous rate infusion (CRI), and 20, 40 and 60 µg/kg/min lignocaine IV, with a bolus of 550 µg/kg preceding each CRI, in 10 Swiss Warmblood horses. Electrically elicited nociceptive withdrawal reflexes were evaluated by deltoid muscle electromyography. Nociceptive threshold and tolerance were determined by electromyography and behaviour following single and repeated stimulation. Plasma concentrations of drugs were determined by liquid chromatography and mass spectrometry. Sedation was scored on a visual analogue scale. Dexmedetomidine increased nociceptive threshold to single and repeated stimulation for all CRIs, except at 2 µg/kg/h, where no increase in single stimulation nociceptive threshold was observed. Dexmedetomidine increased nociceptive tolerance to single and repeated stimulation at all CRIs. There was large individual variability in dexmedetomidine plasma concentrations and levels of sedation; the median plasma concentration providing antinociceptive effects to all recorded parameters was 0.15 ng/mL, with a range from <0.02 ng/mL (below the lower limit of quantification) to 0.25 ng/mL. Lignocaine increased nociceptive threshold and tolerance to single and repeated stimulation at CRIs of 40 and 60 µg/kg/min, corresponding to plasma lignocaine concentrations >600 ng/mL. Only nociceptive tolerance to repeated stimulation increased at 20 µg/kg/min lignocaine. Lignocaine at 40 µg/kg/min and dexmedetomidine at 4 µg/kg/h were the lowest CRIs resulting in consistent antinociception. Lignocaine did not induce significant sedation.

Local anaesthesia for pigs subject to castration

Introduction The legislation in Norway requires that anaesthesia and analgesia must be used when piglets are castrated. The procedure must also be performed by a qualified veterinarian [1]. Since anaesthesia became mandatory in 2002, the injection of the local anaesthetic lidocaine into the testicle has been the preferred anaesthetic method among veterinary practitioners in Norway [2]. The method has been controversial as it has been claimed that the injection in itself was as painful as the castration procedure and that the local anaesthesia did not produce sufficient anaesthesia for surgical castration. This presentation will focus on the published work where the effect of local anaesthesia on piglets during castration was studied.

Physiological evaluation of free-ranging moose (Alces alces) immobilized with etorphine-xylazine-acepromazine in Northern Sweden.

BackgroundEvaluation of physiology during capture and anesthesia of free-ranging wildlife is useful for determining the effect that capture methods have on both ecological research results and animal welfare. This study evaluates capture and anesthesia of moose (Alces alces) with etorphine-xylazine-acepromazine in Northern Sweden.MethodsFifteen adult moose aged 3–15 years were darted from a helicopter with a combination of 3.37 mg etorphine, 75 mg xylazine, and 15 mg acepromazine. Paired arterial blood samples were collected 15 minutes apart with the first sample at 15–23 minutes after darting and were analyzed immediately with an i-STAT®1 Portable Clinical Analyzer.ResultsAll animals developed hypoxemia (PaO2 <10 kPa) with nine animals having marked hypoxemia (PaO2 5.5-8 kPa). All moose were acidemic (ph<7.35) with nine moose having marked acidemia (pH<7.20). For PaCO2, 14 moose had mild hypercapnia (PaCO2 6-8 kPa) and two had marked hypercapnia (PaCO2>8 kPa). Pulse, respiratory rate, pH and HCO3 increased significantly over time from darting whereas lactate decreased.ConclusionsThe hypoxemia found in this study is a strong indication for investigating alternative drug doses or combinations or treatment with supplemental oxygen.

The pharmacokinetics of dexmedetomidine administered as a constant rate infusion in horses.

Dexmedetomidine, the most selective α2-adrenoceptor agonist in clinical use, is increasingly being used in both conscious and anaesthetized horses; however, the pharmacokinetics and sedative effects of this drug administered alone as an infusion are not previously described in horses. Seven horses received an infusion of 8 μg dexmedetomidine/kg/h for 150 min, venous blood samples were collected, and dexmedetomidine concentrations were assayed using liquid chromatography-mass spectrometry (LC/MS) and analyzed using noncompartmental pharmacokinetic analysis. Sedation was scored as the distance from the lower lip of the horse to the ground measured in centimetre. The harmonic mean (SD) plasma elimination half-life (Lambda z half-life) for dexmedetomidine was 20.9 (5.1) min, clearance (Cl) was 0.3 (0.20) L/min/kg, and volume of distribution at steady-state (Vdss ) was 13.7 (7.9) L/kg. There was a considerable individual variation in the concentration of dexmedetomidine vs. time profile. The level of sedation covaried with the plasma concentration of dexmedetomidine. This implies that for clinical use of dexmedetomidine constant rate infusion in conscious horses, infusion rates can be easily adjusted to effect, and this is preferable to an infusion at a predetermined value.

Enantioselective pharmacokinetics of ketoprofen in piglets: the significance of neonatal age

Following intravenous dose of 6mg/kg racemic ketoprofen, the chiral pharmacokinetics of ketoprofen was investigated in eight piglets aged 6 and 21days old. S-ketoprofen predominated over R-ketoprofen in plasma of the piglets in both age groups. The volumes of distribution of S-ketoprofen for the 6- and 21-day-old piglets were 241.7 (211.3-276.5) mL/kg and 155.0 (138.7-173.1) mL/kg, respectively, while the corresponding parameters for R-ketoprofen were 289.2 (250.3-334.2) mL/kg and 193.0 (168.7-220.8) mL/kg. The clearances of R-ketoprofen [948.4 (768.0-1171.2) mL/h/kg and 425 (319.1-566.0) mL/h/kg for the 6- and 21-day-old piglets, respectively] were significantly higher compared to the clearances of S-ketoprofen [57.3 (46.6-70.4) mL/h/kg and 33.8 (27.0-42.2) mL/h/kg for 6- and 21-day-old piglets, respectively]. The elimination half-life of S-ketoprofen was 3.4h for both age groups, while the elimination half-life of R-ketoprofen was 0.2h for the 6-day-old and 0.4h for the 21-day-old piglets. The clearances of both R- and S-ketoprofen were significantly higher in the 6-day-old piglets compared to when they were 21 days old. Furthermore, the volumes of distribution were larger in the youngest age group.