Journal Articles
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Item Pharmacokinetics and effect on renal function and average daily gain in lambs after castration and tail docking, of firocoxib and meloxicam.(Taylor and Francis Group, 2023-07-16) Kongara K; Purchas G; Dukkipati V; Venkatachalam D; Ward N; Hunt H; Speed DAIMS: To evaluate and compare the pharmacokinetics of IM and oral firocoxib, and IM meloxicam, and detect their effect on renal function and average daily gain (ADG) in lambs undergoing tail docking and castration. METHODS: Seventy-five male Romney lambs, aged 3-6 weeks, were randomised into five treatment groups (n = 15 per group): IM firocoxib (1 mg/kg); oral firocoxib (1 mg/kg); IM meloxicam (1 mg/kg); normal saline (approximately 2 mL, oral); or sham. Following the treatment administration, hot-iron tail docking and rubber ring castration were performed in all groups except the sham group, which did not undergo the procedures, but the animals were handled in the same manner as castrated and tail docked lambs. Blood samples were collected before and 1, 2, 4, 6, 8, 24, 48, 72, 96 and 120 hours after treatment administration, and drug concentrations in plasma were quantified by liquid chromatography and mass spectrometry. Plasma urea and creatinine concentrations were determined at a commercial laboratory. Lamb body weights were recorded before and 2, 4 and 8 weeks after tail docking and castration. The pharmacokinetic analysis was carried out using a non-compartmental approach. Between-group and between-time-point differences were compared using mixed model analyses. RESULTS: There was no evidence for a difference in plasma elimination half-life between firocoxib given IM (LSM 18.6 (SE 1.4) hours), firocoxib given orally (LSM 18.2 (SE 1.4) hours), and meloxicam given IM (LSM 17. 0 (SE 1.4) hours). Firocoxib (IM) had a significantly greater volume of distribution (LSM 3.7 (SE 0.2) L/kg) than IM meloxicam (LSM 0.2 (SE 0.2) L/kg). Lambs in the meloxicam group had higher (p < 0.05) plasma urea and creatinine concentrations than those in the firocoxib, saline and sham groups. Lambs' ADG was decreased (p < 0.01) compared to the other treatment groups in the 0-2 week period following meloxicam administration. CONCLUSIONS AND CLINICAL RELEVANCE: Both formulations of firocoxib had a long plasma elimination half-life and large volume of distribution. There was a transient reduction in ADG in the meloxicam group, possibly due to mild renal toxicity. Comparative studies on dose-response effects of firocoxib and meloxicam in lambs following the procedures are required.Item Pharmacokinetics and efficacy of a novel long-acting bupivacaine formulation for cornual nerve block in calves(Frontiers Media S.A., 2022-12-01) Venkatachalam D; Kells N; Chambers P; Jacob A; Ward N; Singh P; Soto-Blanco BLocal anesthetics are commonly used in farm animals to provide analgesia for painful procedures but can cause adverse effects at high systemic concentrations. The pharmacokinetics and efficacy of a long-acting sucrose acetate isobutyrate (SAIB) bupivacaine formulation following cornual nerve block in calves were compared to lidocaine. Fourteen calves were randomly assigned to one of the treatment groups (i) 5% Bupivacaine-SAIB (BUP-SAIB), n = 7; or (ii) 2% lidocaine (LID), n = 7. Cornual nerve block was performed, and duration of effective analgesia was evaluated by nociceptive threshold testing using a hand-held pressure algometer. Blood samples were collected at various time points and plasma concentrations were analyzed by HPLC. Pharmacokinetic parameters were calculated using a non-compartmental model. The mechanical nociceptive thresholds showed that the novel formulation could desensitize the skin around the horn bud for 18.77 ± 8.88 h (range 8-36 h), compared to 0.79 ± 0.34 h (range 0.5-1.5 h) with lidocaine. The mean maximum plasma concentration (Cmax) of bupivacaine was 152.03 (SD 37.34) ng/mL and its Tmax was 0.39 (SD 0.13) h. The half-life of elimination was 32.79 ± 11.00 h and the rate of clearance was 0.12 ± 0.03 L h-1. No toxicity signs were seen after treatment in either group. The novel formulation produced long-lasting analgesia of several times greater duration than that produced by lidocaine. This study showed that the safety and efficacy of the SAIB formulation justifies further studies in a larger population of animals.Item Toxicity and pharmacokinetic studies of lidocaine and its active metabolite, monoethylglycinexylidide, in goat kids(MDPI, 2018-08) Venkatachalam D; Chambers P; Kongara K; Singh PThis 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.Item Pharmacokinetics of articaine hydrochloride and its metabolite articainic acid after subcutaneous administration in red deer (Cervus elaphus)(Taylor & Francis, 23/10/2017) Venkatachalam D; Chambers JP; Kongara K; Singh PAIM: 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.