Impact of oral meloxicam administered alone or in combination with gabapentin on experimentally induced lameness in beef calves

This study examined the pharmacokinetics and analgesic effect of oral meloxicam (MEL) administered alone or in combination with gabapentin (GABA) in an experimental bovine lameness model. Eighteen male British × Continental beef calves aged 4 to 6 mo and weighing 297 to 392 kg were randomly assigned to receive either 1) 0.5 mg/kg lactose monohydrate placebo (PLBO; n = 6), 2) 0.5 mg/kg MEL (n = 6), or 3) 0.5 mg/kg MEL combined with 15 mg/kg GABA (MEL-GABA; n = 6) once daily for 4 d. The first treatment was administered 4 h after a chemical synovitis/arthritis was induced with injection of 15 mg amphotericin B into the left hind lateral distal interphalangeal joint. Changes in activity were evaluated continuously with pedometers. Contact force, contact area, contact pressure, impulse, and stride length were recorded once daily with a pressure mat and visual lameness scores were determined by a masked observer using a 5-point scale. Cortisol and drug concentrations were determined daily by immunoassay and HPLC-mass spectrometry, respectively. Outcomes were compared statistically using a random effects mixed model and analysis of covariance. There was a positive association between lameness scores and serum cortisol concentrations (P = 0.02) and a negative association between lameness score and step count (P \u3c 0.0001), total force (P = 0.001), force applied to the lateral claw (P= 0.02), contact pressure (P = 0.005), and impulse of the lateral claw (P = 0.01). Step count was greater in MEL calves compared with PLBO (P = 0.008) and MEL-GABA (P = 0.04) calves. Impulse was greater in the MEL-GABA calves compared with the PLBO calves (P = 0.03). There was an inverse relationship between plasma MEL concentrations and lameness score (P = 0.02) and a positive association between MEL concentrations and force applied to the lateral claw (P = 0.03), total contact pressure (P = 0.03), and impulse on the lateral claw (P = 0.02). There was a tendency towards a positive association between GABA concentrations, total impulse, and impulse on the lateral claw (P = 0.08) and a negative associate between GABA concentrations and step count (P = 0.08). The results of this study suggest that MEL administered alone or in combination with GABA reduced the severity of lameness in calves following induction of lameness with amphotericin B. These findings have implications for developing analgesic protocols in lame calves that address both production and welfare concerns

Parent-Metabolite Pharmacokinetic Models for Tramadol – Tests of Assumptions and Predictions

Allometric principles were used to discern cross-species differences in (±)-tramadol disposition and formation of its primary analgesic metabolite, (±)-O-desmethyl-tramadol (M1). Species differences in formation of M1 may help predict the analgesic effectiveness of tramadol. Tramadol was administered intravenously by a zero-order (constant infusion) process or rapid bolus dose and racemic concentrations of tramadol and M1 measured. Data were pooled to define differences between species (human, rat, cat, dog, goat, donkey and horse). A two-compartment linear disposition model with first-order elimination was used to describe tramadol and M1 disposition. Slow metabolizers were detected in 6% of the population and tramadol clearance to M1 was 16.2% that of extensive metabolizers. Tramadol clearance to M1 was slower and tramadol clearance by other pathways was faster in rats, dogs, and horses compared to humans. There are substantial differences between species in the pharmacokinetics of tramadol and its M1 metabolite, which are not explained by differences in body weight. The hypothesis that volumes of distribution are similar across species was shown not to be true. M1 exposure in the goat, donkey and cat was comparable to humans, which indicates it is likely to be an effective analgesic at typically used doses in these species but not in dogs or horses

Effects of ropivacaine combined with morphine at 0.15 and 0.2 mg kg-1 in bitches undergoing epidural anesthesia

PURPOSE: To investigate cardiorespiratory effects and serum concentration of ropivacaine combined with morphine at different doses. METHODS: Sixteen healthy adult female dogs weighting 9.8±4.1 kg were included in the study. Twenty minutes after being premedicated with acepromazine and midazolam, the animals were randomly assigned to receive an epidural injection according to each group: RM0.15 = ropivacaine + morphine (0.15 mg kg-1) and RM0.2 = ropivacaine + morphine (0.2 mg kg-1). Variables recorded consisted of: heart rate and cardiac rhythm, respiratory rate, oxyhemoglobin saturation, inspired oxygen fraction, end-tidal carbon dioxide tension, systolic, mean and diastolic arterial pressures, serum cortisol, plasma ropivacaine and morphine. RESULTS: SAP, MAP and DAP were significantly increased at TPR in RM0.15 but returned to normal values at the end of the procedure. Arterial pH was decreased in T30 and TESu in both groups and also returned to acceptable ranges at TR. Both PaO2 and PaCO2 were increased along the duration period of the epidural blockade (T30 and TESu) and returned to acceptable values at TR. Serum cortisol was lower at TB, T30 and TR when compared to TESu. CONCLUSION: The procedures were performed safely and minimal changes in cardiovascular and respiratory variables.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Pró-Reitoria de Pesquisa (ProPe-Unesp)Federal University of Mato Grosso do Sul Faculty of Veterinary Medicine and Animal Science Department of Veterinary MedicineUFMS Faculty of Veterinary Medicine and Animal ScienceSao Paulo State University Faculty of Veterinary MedicineUNESPGaleno Reserch UnitUNESP Faculty of Veterinary Medicine Department of Clinical Surgery and Animal ReproductionSao Paulo State University Faculty of Veterinary MedicineUNESP Faculty of Veterinary Medicine Department of Clinical Surgery and Animal ReproductionFAPESP: 2006/0926

Effects of tramadol on tear production, intraocular pressure, and pupil size in dogs: clinical study

This study aimed to evaluate the effects of tramadol on tear production, intraocular pressure (IOP) and pupil diameter (PD) in healthy dogs. Dogs were randomly assigned to receive 4mg kg-1 (n=11) and 6mg kg-1 (n=11) of tramadol hydrochloride intramuscularly. Tear production (Schirmer tear test, STT-1), IOP (applanation tonometry) and the PD (electronic pachymetry) were assessed before, 30 and 60 minutes after administration of tramadol. Data were compared by analysis of variance for repeated measures (P<0.05). Parameters evaluated before, at 30 and 60min, in dogs treated with 4 and 6mg kg-1, were respectively: (STT-1) 22.50±3.38, 21.14±3.94 and 21.09±2.99mm min-1; and 23.05±3.73,22.64±3.76 and 22.82±3.25mm min-1. (IOP) 18.14±2.68, 17.68±2.59 and 18.23±3.84mmHg; and 19.05±2.27, 18.91±2.74 and 17.64±2.34mmHg. (PD) 6.71±0.65, 7.22±1.42 and 6.90±1.39mm; and 6.25±1.08, 6.80±1.27 and 6.49±0.90mm. All parameters evaluated did not change significantly among time points and dose regimen. Based on the conditions under which the experiments were conducted, tramadol did not affect tear production, IOP and PD in dogs, and could be used as a preoperative analgesic for intraocular surgery and pain control for any cause in patients affected by uveitis, glaucoma and keratoconjunctivitis sicc

Epidural levobupivacaine alone or combined with different morphine doses in bitches under continuous propofol infusion

The aim of this study was to assess the cardiopulmonary, analgesic, adverse effects, serum concentration of cortisol and plasma levels of levobupivacaine and morphine in bitches undergoing propofol anesthesia and epidural analgesia with levobupivacaine alone or combined with morphine. This was a randomized 'blinded' prospective clinical study using 32 adult bitches weighing 9.8±4.1kg that were admitted for elective ovariohysterectomy. Twenty minutes after administration of acepromazine and midazolam, anesthesia was induced with propofol (4mg kg-1) and maintained by a continuous rate infusion (CRI). Each animal was randomly assigned to one of four epidural groups: GL = levobupivacaine alone (0.33mg kg-1); GLM0.1 = levobupivacaine and morphine (0.1mg kg-1); GLM0.15 = levobupivacaine and morphine (0.15mg kg-1); and GLM0.2 = levobupivacaine and morphine (0.2mg kg-1). Variables obtained during anesthesia were heart rate, respiratory rate, systolic, mean and diastolic arterial blood pressures, oxyhemoglobin saturation, inspired oxygen fraction, end-tidal carbon dioxide tension, blood gases, serum cortisol, and plasma levels of levobupivacaine and morphine. The onset and duration times of the blockade were recorded. Arterial pressures were significantly increased in all groups at the times of ovarian pedicle clamping. There was a decrease in pH, together with an increase in both PaO2and PaCO2 over time. Serum cortisol levels were increased in TESu compared to TB, T30 and TR. Limb spasticity, muscle tremors, opisthotonos and diarrhea were observed in some animals during propofol infusion and ceased with the end of CRI. Reactions happened at different moments and lasted for different periods of time in each individual. Epidural with levobupivacaine alone or combined with morphine allowed for ovariohysterectomy to be performed under low propofol infusion rates, with minimal changes in cardiovascular variables and in serum cortisol levels. Adverse effects were observed in very few animals in each group