RESUMEN
AIMS: To evaluate the pharmacokinetics of dexmedetomidine (DEX) administered I/V at a dose of 5â µg/kg bodyweight in dairy calves and to compare the sedative effects of anaesthetic protocols involving DEX and xylazine. METHODS: Nine dairy calves, aged 17-20 days, were treated with 5â µg/kg I/V dexmedetomidine. For pharmacokinetic evaluation, blood samples were collected over 12 hours and serum samples were analysed by high performance liquid chromatography-mass spectrometry. Another nine dairy calves, aged 16-20 days, were treated with 0.2â mg/kg I/V xylazine. After both treatments, heart rate, respiratory rate and rectal temperature were measured for 20 minutes. Sedation quality and recovery times were also assessed. RESULTS: The kinetics of DEX was best described by a two-compartment model. The distribution and elimination half-lives were 8.7 (SD 5.0) and 83.5 (SD 67.5) minutes, respectively. Mean maximum concentration and body clearance were 12.5 (SD 8.6) ng/mL and 27.9 (SD 13.1) mL/minute/kg, respectively; the mean volume of distribution at steady state was 2,170.8 (SD 1,657.5) mL/kg. A decrease in heart rate was observed after treatments with both DEX and xylazine. No differences in heart or respiration rate, or rectal temperature were observed between the two treatment groups. The onset of sedation occurred after 2.7 (SD 0.67) minutes for calves treated with DEX and 2.8 (SD 0.78) minutes for calves treated with xylazine, and was characterised by a similar degree of deep sedation and ease of handling of the calves. All recoveries were eventless, and no adverse reactions were noted. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine treatment resulted in a reliable and long lasting sedation in calves, a transient decrease in heart rate and no modification in respiratory rate or rectal temperature. The results were comparable to xylazine, the most popular alpha-2-agonist among bovine practitioners. The use of DEX in dairy calves for rapid procedures such as dehorning or castration could be suggested.
Asunto(s)
Sedación Consciente/veterinaria , Dexmedetomidina/farmacocinética , Hipnóticos y Sedantes/farmacocinética , Animales , Animales Recién Nacidos , Bovinos , Sedación Consciente/métodos , Dexmedetomidina/sangre , Dexmedetomidina/farmacología , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Hipnóticos y Sedantes/sangre , Hipnóticos y Sedantes/farmacología , Masculino , Frecuencia Respiratoria/efectos de los fármacos , Xilazina/farmacocinética , Xilazina/farmacologíaRESUMEN
The efficacy of enrofloxacin (ENRO) was evaluated against multidrug-resistant avian pathogenic Escherichia coli correlating the minimum inhibitory concentrations (MIC) of 235 E. coli field strains with its pharmacokinetics (PK) in 50 healthy turkeys (5 groups) with a PK/pharmacodynamic approach. The treatments were as follows: a) single oral gavage and b) single subcutaneous (SC) treatment at the recommended dose of 10 mg/kg; c) single oral gavage, d) 5 d of 10-h pulsed water medication, and e) 5 d of 24-h continuous water medication at the doubled dose of 20 mg/kg. Blood samples were collected at established times over 24 h. Plasma was analyzed using a liquid chromatography tandem mass spectrometry method that was validated in house. A monocompartmental and a noncompartmental model were applied to the data to obtain the PK results. After gavage administration, the mean maximum concentration Cmax/MIC50 and area under the curve AUC0-24/MIC50 ratios were, respectively, 3.07 ± 0.62 and 7.01 ± 1.03 and 25.48 ± 3.04 and 57.2 ± 3.73 for the 10 and 20 mg/kg doses, respectively. After SC administration of 10 mg/kg, Cmax/MIC50 and AUC0-24/MIC50 ratios were 3.45 ± 0.75 and 33.96 ± 7.46, respectively. After the administration of 10-h pulsed or 24-h continuous medicated water at 20 mg/kg, lower values of Cmax/MIC50 (10-h pulsed: 3.45 ± 0.7; 24-h continuous: 3.05 ± 0.48) and AUC0-24/MIC50 (10-h pulsed: 42.42 ± 6.17; 24-h continuous: 53.32 ± 5.55) were obtained. Based on these results, the European Union-recommended dosage of 10 mg/kg seems ineffective to achieve adequate drug plasma concentrations and even the 20 mg/kg by 10 h pulsed or continuous medicated water administration did not reach completely efficacious concentrations in plasma against colibacillosis. Although the results obtained were not completely encouraging, the medicated water should preferably be provided continuously. To conclude about the efficacy of ENRO treatment against colibacillosis, target tissue concentration should be extensively considered.
Asunto(s)
Antibacterianos/farmacología , Infecciones por Escherichia coli/veterinaria , Fluoroquinolonas/farmacología , Enfermedades de las Aves de Corral/tratamiento farmacológico , Pavos , Animales , Antibacterianos/farmacocinética , Área Bajo la Curva , Cromatografía Liquida/veterinaria , Relación Dosis-Respuesta a Droga , Enrofloxacina , Escherichia coli/efectos de los fármacos , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Femenino , Fluoroquinolonas/farmacocinética , Pruebas de Sensibilidad Microbiana/veterinaria , Enfermedades de las Aves de Corral/microbiología , Espectrometría de Masas en Tándem/veterinariaRESUMEN
Flumequine (FLU) is used in the treatment of systemic bacterial infections in poultry, including colibacillosis, which is a common disease in turkeys. The pharmacokinetic (PK) behavior of FLU administered to 32 healthy turkeys as an oral bolus via gavage or as 10-h pulsed administration in drinking water were compared, using the authorized dose of 15 mg/kg and the double dose of 30 mg/kg. The minimum inhibitory concentrations (MIC) of 235 Escherichia coli field strains isolated from poultry were determined for pharmacodynamics (PD) to develop a PK/PD model. Blood samples were collected at established times over 24 h, and the obtained plasma was analyzed using a liquid chromatography tandem mass spectrometry method that was validated in-house. A monocompartmental model and a noncompartmental model were applied to the data to obtain the PK results. For both types of administration and both dosages, the ratios of the maximum concentration (Cmax)/MIC50 and the area under the plasma concentration-time curve (AUC)/MIC50 achieved were considerably lower than the fluoroquinolone breakpoints usually adopted for efficacy. The Cmax/MIC50 and AUC0-24/MIC50 ratios were, respectively, 0.67 ± 0.09 and 4.76 ± 0.48 and 1.18 ± 0.35 and 7.05 ± 2.40 for the 15 and 30 mg/kg bolus doses, respectively. After 10-h pulsed administration of 15 mg/kg, values of Cmax/MIC50, 0.19 ± 0.02 on d 1 and 0.30 ± 0.08 on d 5 of therapy were obtained, the AUC/MIC50 ratios were 2.09 ± 0.29 and 3.22 ± 0.93 on d 1 and 5, respectively. Higher values were obtained with the doubled dose of 30 mg/kg: the Cmax/MIC50 ratios were 0.49 ± 0.11 on d 1 and 0.69 ± 0.18 on d 5; the AUC/MIC50 ratios were 5.15 ± 1.15 and 6.57 ± 1.92 on d 1 and 5, respectively. Based on these results, FLU administration should be adopted when specific diagnostic findings indicate its efficacy, and revising the dosage scheme to comply with the prudent and responsible use of antimicrobials in veterinary medicine is advisable.
Asunto(s)
Antibacterianos/farmacología , Infecciones por Escherichia coli/veterinaria , Escherichia coli/efectos de los fármacos , Fluoroquinolonas/farmacología , Enfermedades de las Aves de Corral/tratamiento farmacológico , Pavos , Administración Oral , Animales , Antibacterianos/sangre , Antibacterianos/farmacocinética , Área Bajo la Curva , Cromatografía Liquida/veterinaria , Relación Dosis-Respuesta a Droga , Infecciones por Escherichia coli/tratamiento farmacológico , Femenino , Fluoroquinolonas/sangre , Fluoroquinolonas/farmacocinética , Pruebas de Sensibilidad Microbiana/veterinaria , Espectrometría de Masa por Ionización de Electrospray/veterinariaRESUMEN
Tilmicosin (TIM, Pulmotil) was administered to eight rabbits by oral gavage at a dose of 12.5 mg/kg body weight for 2, 5, and 7 days, and its plasma kinetics and intrapulmonary disposition were investigated. TIM concentrations in plasma samples collected after days 1 and 6 of treatment were measured by high-performance liquid chromatography with ultraviolet detection. The pharmacokinetic parameters, obtained by non-compartmental analysis of TIM plasma concentrations, did not show any significant variations between days 1 and 6. From the second day of treatment, TIM concentrations attained in lung tissue and pulmonary alveolar macrophages (PAM) exceeded those in plasma by 7- and 400-fold, respectively, and high levels were maintained in lung tissues during the entire treatment duration. After the first day of withdrawal, a fast decline in TIM levels in both plasma and lung tissue was observed, but in PAM, much higher concentrations were maintained after 3 days of TIM withdrawal.