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.

Our objective was to assess the pharmacokinetic characteristics of metamizole when administered together with tramadol in a single intravenous dose to donkeys. Ten male animals received 10 mg∙kg⁻¹ of dipyrone associated with 2 mg∙kg⁻¹ of tramadol (T₂M₁₀) and 25 mg∙kg⁻¹ of dipyrone with 2 mg∙kg⁻¹ of tramadol (T₂M₂₅). Venous blood samples were taken from groups to determine the pharmacokinetics after drug administration, using initial brief intervals that were followed by extended periods until 48 h. Restlessness and ataxia were observed in two animals in the T₂M₂₅ group. Analysis revealed prolonged detectability of tramadol, 4-methylamine antipyrine, 4-aminoantipyrine (up to 24 h), and O-desmethyltramadol (up to 12 h) after administration. Although metamizole and its metabolites showed no significant pharmacokinetic changes, tramadol and O-desmethyltramadol exhibited altered profiles, likely because of competition for the active sites of CYP450 enzymes. Importantly, the co-administration of metamizole increased the bioavailability of tramadol and O-desmethyltramadol in a dose-dependent manner, highlighting their potential interactions and emphasizing the need for further dose optimization in donkey analgesic therapies. In conclusion, metamizole co-administered with tramadol interferes with metabolism and this interference can change the frequency of drug administration and its analgesic efficacy.