Preet Singh

Pharmacokinetics of butorphanol in broiler chickens

Butorphanol tartrate (2 mg/kg) was injected intravenously in 18 healthy broiler chickens to study its pharmacokinetics. Plasma samples were analysed by a highly sensitive high-performance liquid chromatography with diode-array detection method and pharmacokinetic parameters were calculated from the mean pooled data. With non-compartmental analysis, the terminal half-life (T1/2.z) was 71.3 minutes, clearance was 67.6 ml/minute/kg and the apparent volume of distribution was 6.9 l/kg. The concentration-time curve was also fitted to a two-compartmental model. In this analysis, elimination half-life (T1/2β) was 69.3 minutes, clearance was 74.6 ml/minute/kg and volume of distribution at steady state was 5.6 l/kg. The micro rate constants k21, k12 and k10 were 0.034, 0.050 and 0.029, respectively. Butorphanol was well distributed in the chickens with rapid clearance. It remained above the minimum effective concentration for analgesia in mammals for approximately two hours in the chickens.

Analgesic effects of morphine and butorphanol in broiler chickens

OBJECTIVE To evaluate analgesic efficacies of morphine and butorphanol in lame broiler chickens. STUDY DESIGN Double blind, randomized, controlled experimental study. ANIMALS In study 1, 36 lame and 36 sound chickens. In study 2, 48 lame and 48 sound chickens. METHODS Sound and lame chickens were gait scored and randomly assigned into four groups: sound-drug, sound-placebo, lame-drug, and lame-placebo in study 1. In study 2, an additional lame and sound handling control group was included. Chickens in drug groups were injected with either morphine or butorphanol 2 mg kg-1 intravenously. Chickens in placebo groups were injected with an equal volume of normal saline. All birds underwent an obstacle course (OC) and latency-to-lie (LTL) test before injection and at 30 minutes and 2 hours after injection, to assess their walking ability and their standing ability. The time taken to finish the OC and the standing time in the LTL test were recorded. Friedman tests with Dunns correction were used to identify significant differences. RESULTS Lame chickens finished the OC faster (mean ± standard deviation 36 ± 8 c.f. 69 ± 18 seconds) after the injection of butorphanol. Morphine caused sedation with an increase in time taken to finish the OC, even in sound chickens. In the lame handling control and placebo groups the OC times increased and the LTL times decreased with each observation. CONCLUSION Intravenous butorphanol (2 mg kg-1) may be analgesic in chickens for up to 2 hours. Morphine caused sedation.

A comparison of two different ketamine and diazepam combinations with an alphaxalone and medetomidine combination for induction of anaesthesia in sheep

Abstract AIMS: To investigate the perceived adverse effects of a particular batch of ketamine during induction of anaesthesia in sheep and to assess if any adverse effects would make intubation more difficult for the veterinary students. METHODS: Thirty adult sheep (mean bodyweight 74.5 (SD 9.4) kg) were randomly assigned to one of six groups of five sheep. Sheep in Groups A and B received I/V 0.5 mg/kg diazepam and 10 mg/kg ketamine (Ketamine Injection; Parnell Laboratories NZ Ltd, of the suspect batch); those in Groups C and D received I/V 0.5 mg/kg diazepam and 10 mg/kg ketamine (Ketalar; Hospira NZ Ltd.), and those in Groups E and F received I/V 2 μg/kg medetomidine and 2 mg/kg alphaxalone. In Groups A, C and E, intubation was by an experienced anaesthetist, and in Groups B, D and F intubation was by a veterinary student. Time from injection to successful intubation, the ease of intubation, saturation of haemoglobin with oxygen (SpO2) and partial pressure of oxygen in arterial blood (PaO2) were measured before the sheep were connected to an anaesthetic machine and allowed to breath oxygen. Times to extubation, holding its head up and standing, maximum and minimum heart rates, respiratory rates, maximal end tidal CO2, and the quality of recovery were then recorded. RESULTS: There were no measurable differences in outcomes between sheep in Groups A and B compared with C and D. Time to intubation was slightly shorter for the experienced anaesthetist than the student, but the difference was not significant. The sheep in Groups E and F took less time to recover than those in Groups A−D (p<0.05), but there were no significant differences between the groups in either the ease of induction or quality of recovery. Most sheep in Groups E and F showed minor excitatory effects, mainly at induction, which did not interfere with induction. Respiratory rates were lower in Groups E and F than Groups A−D (p<0.01), but SpO2 was higher in Groups E and F than A and B (p<0.05). CONCLUSIONS: The clinical impression that the batch of Parnell ketamine produced unexpected effects was shown to be incorrect. All the combinations produced anaesthesia that allowed intubation by the veterinary student. CLINICAL RELEVANCE: All the drug combinations produced satisfactory anaesthesia in sheep, but the alphaxaloneand medetomidine combination resulted in faster recovery.

Plasma Concentration of Butorphanol in Northern Royal Albatross Undergoing Fracture Repair

Aims: The objective of this study was to determine the plasma concentration of butorphanol injected intravenously at 4mg/kg dose in Northern Royal Albatross and compare the pharmacokinetic parameters with that of broiler chickens. Methods: The plasma concentration of butorphanol was analysed by High Performance Liquid Chromatography. The pharmacokinetic parameters were calculated by non-compartmental approach using standard equations in spreadsheet. Results: The half-life, volume of distribution, clearance, mean residence time were 94.4 minutes, 860.5 ml/kg, 6.31 ml/kg/min, and 146.4 minutes, respectively. The levels remained above the minimum effective concentration for mammals for about 4 hours. Conclusion: Though we have data from only one albatross for butorphanol kinetics, it confirms the chicken data: butorphanol does not last as long in birds as in mammals. This shows that dose regimes for mammals are unsuitable for injured wild birds, but we can use chickens as a model for other wild bird species. The levels remained above the minimum effective concentration for mammals Clinical Relevance: Butorphanol can provide good post operative analgesia in wild birds. The broiler chickens may be used as a model of drug research for wild birds, but further work is required to establish this fact. Received: 28 February, 2018; Accepted: 13 March, 2018; Published: 16 March, 2018 *Corresponding author: Preet Singh, Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Tennant Drive, Palmerston North New Zealand. Tel: +6463569099 E-mail: P.M.Singh@massey.ac.nz

Pharmacokinetics of articaine hydrochloride and its metabolite articainic acid after subcutaneous administration in red deer (Cervus elaphus)

AIM: To develop and validate a simple and sensitive method using liquid chromatography-mass spectrometry (LC-MS) for quantification of articaine, and its major metabolite articainic acid, in plasma of red deer (Cervus elaphus), and to investigate the pharmacokinetics of articaine hydrochloride and articainic acid in red deer following S/C administration of articaine hydrochloride as a complete ring block around the antler pedicle. METHODS: The LC-MS method was validated by determining linearity, sensitivity, recovery, carry-over and repeatability. Articaine hydrochloride (40 mg/mL) was administered S/C to six healthy male red deer, at a dose of 1 mL/cm of pedicle circumference, as a complete ring block around the base of each antler. Blood samples were collected at various times over the following 12 hours. Concentrations in plasma of articaine and articainic acid were quantified using the validated LC-MS method. Pharmacokinetic parameters of articaine and articainic acid were estimated using non-compartmental analysis. RESULTS: Calibration curves were linear for both articaine and articainic acid. The limits of quantifications for articaine and articainic acid were 5 and 10 ng/mL, respectively. Extraction recoveries were >72% for articaine and >68% for articainic acid. After S/C administration as a ring block around the base of each antler, mean maximum concentrations in plasma (Cmax) of articaine were 1,013.9 (SD 510.1) ng/mL, detected at 0.17 (SD 0.00) hours, and the Cmax for articainic acid was 762.6 (SD 95.4) ng/mL at 0.50 (SD 0.00) hours. The elimination half-lives of articaine hydrochloride and articainic acid were 1.12 (SD 0.17) and 0.90 (SD 0.07) hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The LC-MS method used for the quantification of articaine and its metabolite articainic acid in the plasma of red deer was simple, accurate and sensitive. Articaine hydrochloride was rapidly absorbed, hydrolysed to its inactive metabolite articainic acid, and eliminated following S/C administration as a ring block in red deer. These favourable pharmacokinetic properties suggest that articaine hydrochloride should be tested for efficacy as a local anaesthetic in red deer for removal of velvet antlers. Further studies to evaluate the safety and residues of articaine hydrochloride and articainic acid are required before articaine can be recommended for use as a local anaesthetic for this purpose.

Toxicity and Pharmacokinetic Studies of Lidocaine and Its Active Metabolite, Monoethylglycinexylidide, in Goat Kids

Simple Summary Disbudding is becoming a routine husbandry procedure in goat farms even though it is a painful procedure without appropriate pain relief. One of the ways to alleviate or minimize the pain associated with disbudding is by using local anesthetics like lidocaine hydrochloride. However, lidocaine hydrochloride has been reported to be toxic in goat kids and there is some data regarding the doses that produce toxicity in goat kids. Therefore, the research team studied the toxicity and pharmacokinetics of lidocaine hydrochloride in goat kids to recommend a safe dose for disbudding. Abstract This study determined the convulsant plasma concentrations and pharmacokinetic parameters following cornual nerve block and compared the results to recommend a safe dose of lidocaine hydrochloride for goat kids. The plasma concentrations of lidocaine and monoethylglycinexylidide (MGX) were quantified using liquid chromatography-mass spectrometry. A total dose of 7 mg/kg body weight (BW) was tolerated and should therefore be safe for local and regional anesthesia in goat kids. The mean plasma concentration and mean total dose that produced convulsions in goat kids were 13.59 ± 2.34 µg/mL and 12.31 ± 1.42 mg/kg BW (mean ± S.D.), respectively. The absorption of lidocaine following subcutaneous administration was rapid with Cmax and Tmax of 2.12 ± 0.81 µg/mL and 0.33 ± 0.11 h, respectively. The elimination half-lives (t½λz) of lidocaine hydrochloride and MGX were 1.71 ± 0.51 h and 3.19 ± 1.21 h, respectively. Injection of 1% lidocaine hydrochloride (0.5 mL/site) was safe and effective in blocking the nerves supplying horn buds in goat kids.

Remotely operated mechanical nociceptive device for sheep: Preliminary investigations

The objective of this study was to design and assemble a remotely operated mechanical nociceptive device for testing pain thresholds in sheep. This device was assembled by using an actuator connected to a load cell. The linear movement of the actuator was converted into an orthogonal movement using a bell crank mechanism. The assembly was then strapped on the distal forelimb of the sheep (below the carpus joint). The activation of this device resulted in the movement of a blunt pin pressing on the skin of the carpal region of the sheep. The force required to generate a nociceptive response on sheep was recorded using the load cell. The force data is transferred to a computer using a WiFi module and then displayed on the Graphical User Interface. The results from the pilot study on two sheep indicated that force of 4 to 6 Newton is required to generate a pain response. The variation of measured force, after multiple observations on two sheep, was less compared to the previous nociceptive devices used. Further work is required to validate this device for its use in veterinary pain research. This device has potential in testing efficacy of analgesic drugs in farm animals including sheep and cattle.

Thalidomide pharmacokinetics in sheep

Abstract AIM: To determine the half life (T1/2), time taken to reach maximum plasma concentration (Tmax) and maximum plasma concentration (Cmax) of thalidomide in sheep following I/V, oral and topical treatment with a single dose of thalidomide. METHOD: Three groups of 4–6-month-old ram lambs were treated with thalidomide dissolved in dimethylsulphoxide (DMSO). The first group (n=10) was treated I/V with 100 mg thalidomide in 2 mL DMSO; the second group (n=8) received 400 mg thalidomide in 2 mL DMSO orally, and the third group (n=8) had 400 mg thalidomide in 4 mL DMSO applied topically. Plasma samples were collected up to 36 hours after treatment, snap-frozen at −80°C and analysed for concentrations of thalidomide using high performance liquid chromatography. RESULTS: Following I/V administration, T1/2 was 5.0 (SEM 0.4) hours, volume of distribution was 3,372.0 (SEM 244.3) mL/kg and clearance was 487.1 (SEM 46.1) mL/hour.kg. Topical application of 400 mg thalidomide did not increase plasma concentrations. Following oral administration, thalidomide bioavailability was 89%, with T1/2, Tmax, and Cmax being 7.2 (SEM 0.8) hours, 3.0 (SEM 0.4) hours and 1,767.3 (SEM 178.1) ng/mL, respectively. CONCLUSION: Topical administration using DMSO as a solvent did not increase concentrations of thalidomide in plasma. The mean pharmacokinetic parameters determined following oral treatment with 400 mg of thalidomide were similar to those reported in humans receiving a single 400 mg oral dose (T1/2 7.3 hours; Tmax 4.3 hours and Cmax 2,820 ng/mL). There is potential for thalidomide to be used as a model for the treatment of chronic inflammatory conditions in sheep, such as Johnes disease, where tumour necrosis factor alpha plays a pathogenic role.