This study investigated the pharmacokinetic profile of and pharmacodynamic response to dexmedetomidine administered intramuscularly (IM) at a dose of 10 μg/kg in healthy cats. Nine adult cats were evaluated before and after administration of the drug, with serial collections of plasma samples. Dexmedetomidine induced deep sedation, with a rapid onset of action and a duration of one hour, reaching a peak between 20 and 30 min after administration. The half-life (T½) was 70.2 ± 48 min, with a maximum concentration (Cmax) of 2.2 ± 1.9 ng/mL and time to reach maximum concentration (Tmax) of 26.4 ± 19.8 min. The area under the curve (AUC) was 167.1 ± 149.1 ng/mL*min, with a volume of distribution (Vd) of 2159.9 ± 3237.8 mL/kg and clearance (Cl) of 25.8 ± 33.0 mL/min/kg. There was a reduction in heart rate (HR) and respiratory rate (RR) in relation to the baseline, with a slight decrease in systolic (SBP), diastolic (DBP), and mean (MAP) blood pressure in the first hour. Blood glucose increased after 60 min. Dexmedetomidine proved to be effective and safe, with rapid absorption, metabolization, and elimination, promoting good sedation with minimal adverse effects after IM administration in healthy cats.

Ten northeast Brazilian donkeys were used to evaluate the influence of meteorological variables on their physiological responses in tropical conditions. Physiological data included respiratory rate (RR), heart rate (HR), rectal temperature (RT), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and cortisol concentrations. The environment was characterized using the following meteorological variables: air temperature (AT), relative humidity (RH) and wind speed (WS). The variables were organized into time. The performed statistical tests included correlations, multivariate and variance analysis. The RR variable was lower in the period between 7 pm and 10 am associated with a decreased RT in the same period. Differences were not detected within each time group of the day for the HR, cortisol concentrations, SBP, DBP and MAP. The physiological traits of the animals in this study were not affected by the time of the day according to the principal component analysis. Significant results were found in the correlation analysis between the RR physiological variable and the meteorological variables of RH (−0.66) and WS (0.69). Thermoregulation mechanisms exhibit few daily cyclical variations; therefore, the northeast Brazilian donkeys have little physiological responses influenced by environmental factors in the semi-arid region.

This study aimed to determine the pharmacokinetic profile of the active dipyrone metabolites, 4-methylaminoantipyrine and 4-aminoantipyrine, following intravenous administration in dogs. Eleven mixed-breed dogs received a 25 mg·kg⁻¹ dipyrone dose and blood samples were collected at 0, 5, 15, 30 and 45 min, as well as at 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 h. Plasma concentrations of both metabolites were analyzed by ultra-performance liquid chromatography coupled to mass spectrometry. The PKSolver 2.0 and GraphPad Prisma 10 software programs were used for pharmacokinetic and statistical analyses, applying a Principal Component Analysis for MAA and descriptive statistics for both metabolites. Two groups were noteworthy concerning MAA: slow metabolizers (SM) and normal/rapid metabolizers (NM). Significant differences were observed between half-life (T_½) and MRT_{0_inf obs} values between the MAA groups. The T_½ and MRT_{0_info obs} were 44.44 ± 11.74 and 32.62 ± 16.53 h for the SM group and 11.25 ± 5.37 and 7.44 ± 4.25 h for the NM group, respectively. The C_max of AA was 2.80 ± 1.43 µg mL⁻¹. Metabolites were detectable for 48 h in all animals for MAA and seven for AA. These findings suggest that metamizole reaches analgesia plasma concentrations associated with cyclooxygenase inhibition with few adverse effects in dogs. However, additional pharmacogenetic and pharmacotherapeutic monitoring studies are required.

This study aimed to determine the pharmacokinetic profile of two active metabolites of metamizole (dipyrone), N-methyl-4-aminoanthypyrine and 4-aminoanthypyrine, after intravenous administration in cats. Eight healthy mixed-breed cats were intravenously administered metamizole (25 mg/kg). Blood samples were collected at predetermined time points for up to 48 h after administration. Information on behavioral changes in the animals and adverse effects was collected. Plasma aliquots were processed and analyzed using the ultra-performance liquid chromatography tandem mass spectrometry technique. Salivation was identified as an adverse clinical sign. The mean maximal plasma concentrations of N-methyl-4-aminoanthypyrine and 4-aminoanthypyrine were 29.31 ± 24.57 μg/mL and 1.69 ± 0.36 μg/mL, with half-lives of around 4.98 and 14 hr, respectively. The area under the plasma concentration curve values were 28.54 ± 11.33 and 49.54 ± 11.38 h*µg/mL for N-methyl-4-aminoanthypyrine and 4-aminoanthypyrine, respectively. The plasma concentration of N-methyl-4-aminoanthypyrine was detectable for up to 24 h and was smaller than 4-aminoanthypyrine. 4-aminoanthypyrine was detectable for more than 48 h. Results suggest that metamizole is converted into active metabolites in cats, similar to findings in humans. A validated UPLC-MS/MS method was used to characterize the pharmacokinetics of N-methyl-4-aminoanthypyrine and 4-aminoanthypyrine. Further PK/PD and safety studies should be performed before defining the dose or administration intervals for clinical use.

A anestesia locorregional reduz o requerimento de agentes inalatórios e diminui as respostas autonômicas a estímulos cirúrgicos nocivos. Objetiva-se descrever um bloqueio anestésico do plexo braquial guiado por neuroestimulador em jumento, submetido à amputação do membro anterior direito. Foi realizada medicação pré-anestésica com detomidina 0,01mg.kg^-1, indução com diazepam 0,05mg.kg^-1 e cetamina 2mg.kg^-1, todos pela via intravenosa (IV), e a manutenção da anestesia com isoflurano. O plexo braquial foi bloqueado por acesso subescapular, sendo usado neuroestimulador. Utilizou-se 1mg.kg^-1 de bupivacaína 0,5% sem vasoconstritor, associada a 1mg.kg^-1 de lidocaína 2% sem vasoconstrictor. Os valores de FC e ƒ durante o procedimento cirúrgico variaram de 62 a 78bpm e de 24 a 32rpm, respectivamente. Foram coletadas quatro amostras de sangue para dosagem de cortisol. Este, antes da aplicação da medicação pré-anestésica, foi de 6,4μg/dL e, 30 minutos após a MPA, foi de 2,8μg/dL. A recuperação anestésica foi rápida e sem complicações. O bloqueio do plexo braquial guiado por neuroestimulador mostrou-se eficaz em jumentos, fornecendo analgesia e anestesia satisfatória.

Tramadol exposure after low oral doses is variable in dogs, and the estimation of the terminal phase can be difficult when late concentrations plateau or rebound. This study characterized tramadol and O‐desmethyltramadol (M1) after a single oral dose of 2 mg/kg in 10 healthy female mixed‐breed dogs. Plasma was collected from 0 to 48 h and analysed by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Non‐compartmental analysis was performed for each animal. The terminal slope was evaluated using at least three quantifiable post‐peak observations, and λz was not forced when a coherent log‐linear decline was absent. Mean maximum observed concentration ( C _max ) and area under the concentration–time curve from time zero to the last quantifiable concentration (AUC0–last) for tramadol were 434.53 ± 337.68 ng/mL and 1748.40 ± 1370.05 h·ng/mL, respectively; median time to maximum observed concentration ( T _max ) was 1.5 h (range, 0.5–2.0 h). For M1, mean C _max and AUC0–last were 6.53 ± 3.26 ng/mL and 34.86 ± 28.55 h·ng/mL, respectively; median T _max was 1.0 h (0.5–2.0 h). A terminal phase was retained in seven of 10 profiles for each analyte. In these profiles, mean terminal half‐life was 15.53 ± 10.69 h for tramadol and 12.65 ± 11.55 h for M1. Three analyte profiles lacked a defensible terminal phase. We excluded quantitative pharmacokinetic analysis of M2 and M5 because authentic analytical standards were unavailable. Oral tramadol at 2 mg/kg was rapidly absorbed, but systemic exposure varied markedly among dogs. Based on the retained terminal half‐life estimates, a 12‐h dosing interval may be pharmacokinetically plausible for future multiple‐dose studies but should not be considered a validated clinical recommendation.