Plasma pharmacokinetics tissue concentration and urine elimination after cephalotin intravenous administration to cats under surgical conditions

Pharmacokinetic profile, tissue concentrations and urine elimination of cephalothin in cats under surgical conditions after a single intravenous dose (30 mg/kg) were studied. Initial plasma concentrations were high (Cp(0), 353.79±118.92 μg/mL), with fast and moderately wide distribution (T1⁄2(d) 0.14±0.10 h) (V(d(ss)) 0.19±0.03 L/kg) and rapid elimination (ClB, 0.16±0.03 L/h.kg; T1⁄2, 1.07±0.23 h; MRT, 1.16±0.21 h). Thirty to 60 minutes after intravenous administration, cephalothin tissue concentrations were in the range of 3.73 μg/g (testicle tissue) to 25.63 μg/g (uterus). Tissue/plasma concentrations rate was in a range of 0.04 (testicle) to 0.21 (uterus). Cephalothin urine elimination was 66.49% in the first 6 hours after administration. Cephalothin plasma concentrations remained above a MIC≥1μg/mL up to 5.5 hours in all the studied cats. However, for MIC≥8μg/mL (MIC breakpoint) this time is reduced to 2.5 hours. This suggests that proper perioperative prophylactic use of cephalothin in cats requires a dose interval not longer than 2 hours.Fil: Albarellos, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Montoya, Laura. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Lupi, Martin Pablo. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Passini, Sabrina Mariela. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Lorenzini, Paula Mercedes. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Landoni, Maria Fabiana. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Cefuroxime plasma pharmacokinetics, tissue and urine concentrations after parenteral administration to cats

Cefuroxima es una cefalosporina de segunda generación que incluye en su espectro antibiótico a cocos gram-positivos, bacilos gram-negativos y anaerobios. El objetivo de este trabajo es caracterizar la farmacocinética plasmática de cefuroxima en gatos luego de su administración por vía intravenosa, intramuscular y subcutánea, y determinar la concentración de cefuroximaen algunos tejidos y en la orina de los animales. Luego de la administración del antibiótico (20 mg/kg), se tomaron muestras sanguíneas y de orina durante 8 horas y muestras de tejidos entre las 1-1,5 horas. Los principales parámetros farmacocinéticos (media±desvío estándar) para la administración intravenosa fueron: concentración inicial (μg/mL): 135,46±81,42; vidamedia de eliminación (h): 0,21±0,15. Para las administraciones intramuscular y subcutánea los principales parámetros farmacocinéticos fueron respectivamente: concentración máxima (μg/mL): 48,65±6,71 y 28,17±8,44, tiempo de la concentración máxima (h): 0,18±0,06 y 0,82±0,30, y vida media de eliminación (h): 1,04±0,10 y 1,59±0,18. Las concentraciones (μg/g) en tejidos estuvieron entre 3, 35±0,65 y 23.02±8.77. Al cabo de 8 horas se recuperó enla orina el 78,09±24,59% de la dosis administrada. Estos resultados indicarían que cefuroxima administrada a una dosis de 20 mg/kg por las vías estudiadas sería de utilidad para el tratamiento de infecciones producidas por microorganismos susceptibles en gatos.Cefuroxime is a second generation cephalosporin active against gram-positive cocci, gramnegative rods and anaerobes. The aim of the present study is to characterize cefuroxime plasma pharmacokinetics after intravenous, intramuscular and subcutaneous administration to cats; and, to determine cefuroxime concentrations in some tissues and in urine of the animals. After antibiotic administration (20 mg/kg), blood and urine samples were taken during 8 hours and, tissue samples at 1-1.5 hours. After intravenous administration, main pharmacokinetic parameters (mean±SD) were: initial plasma concentration (µg/mL): 135.46±81.42; half-life (h): 0.21±0.15. After intramuscular and subcutaneous administration, main pharmacokinetic parameters were, respectively: maximum plasma concentrations (µg/mL): 48.65±6.71 and 28.17±8.44; time of maximum plasma concentration were 0.18±0.06 h and 0.82±0.30 h; and, elimination half-life (h): 1.04±0.10 and 1.59±0.18. Tissue concentrations (µg/g) ranged between 3,35±0,65 and 23.02±8.77. After 8 hours, 78,09±24,59% of the administered cefuroxime was recovered from urine. The present results showed that cefuroxime, administered at a dosage of 20 mg/kg by intravenous, intramuscular or subcutaneous route, would be a useful tool for the infection treatment in cats when produced by susceptible microorganisms.Facultad de Ciencias Veterinaria

Cefuroxime plasma pharmacokinetics, tissue and urine concentrations after parenteral administration to cats

Cefuroxima es una cefalosporina de segunda generación que incluye en su espectro antibiótico a cocos gram-positivos, bacilos gram-negativos y anaerobios. El objetivo de este trabajo es caracterizar la farmacocinética plasmática de cefuroxima en gatos luego de su administración por vía intravenosa, intramuscular y subcutánea, y determinar la concentración de cefuroximaen algunos tejidos y en la orina de los animales. Luego de la administración del antibiótico (20 mg/kg), se tomaron muestras sanguíneas y de orina durante 8 horas y muestras de tejidos entre las 1-1,5 horas. Los principales parámetros farmacocinéticos (media±desvío estándar) para la administración intravenosa fueron: concentración inicial (μg/mL): 135,46±81,42; vidamedia de eliminación (h): 0,21±0,15. Para las administraciones intramuscular y subcutánea los principales parámetros farmacocinéticos fueron respectivamente: concentración máxima (μg/mL): 48,65±6,71 y 28,17±8,44, tiempo de la concentración máxima (h): 0,18±0,06 y 0,82±0,30, y vida media de eliminación (h): 1,04±0,10 y 1,59±0,18. Las concentraciones (μg/g) en tejidos estuvieron entre 3, 35±0,65 y 23.02±8.77. Al cabo de 8 horas se recuperó enla orina el 78,09±24,59% de la dosis administrada. Estos resultados indicarían que cefuroxima administrada a una dosis de 20 mg/kg por las vías estudiadas sería de utilidad para el tratamiento de infecciones producidas por microorganismos susceptibles en gatos.Cefuroxime is a second generation cephalosporin active against gram-positive cocci, gramnegative rods and anaerobes. The aim of the present study is to characterize cefuroxime plasma pharmacokinetics after intravenous, intramuscular and subcutaneous administration to cats; and, to determine cefuroxime concentrations in some tissues and in urine of the animals. After antibiotic administration (20 mg/kg), blood and urine samples were taken during 8 hours and, tissue samples at 1-1.5 hours. After intravenous administration, main pharmacokinetic parameters (mean±SD) were: initial plasma concentration (µg/mL): 135.46±81.42; half-life (h): 0.21±0.15. After intramuscular and subcutaneous administration, main pharmacokinetic parameters were, respectively: maximum plasma concentrations (µg/mL): 48.65±6.71 and 28.17±8.44; time of maximum plasma concentration were 0.18±0.06 h and 0.82±0.30 h; and, elimination half-life (h): 1.04±0.10 and 1.59±0.18. Tissue concentrations (µg/g) ranged between 3,35±0,65 and 23.02±8.77. After 8 hours, 78,09±24,59% of the administered cefuroxime was recovered from urine. The present results showed that cefuroxime, administered at a dosage of 20 mg/kg by intravenous, intramuscular or subcutaneous route, would be a useful tool for the infection treatment in cats when produced by susceptible microorganisms.Facultad de Ciencias Veterinaria

Plasma and tissue clindamycin antimicrobial activity after parenteral administration to cats under surgical conditions

Clindamycin plasma and tissue disposition in cats under surgical conditions after a single intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration at a dose rate of 10 mg/kg were studied. After intravenous, intramuscular and subcutaneous administration, peak plasma concentrations were 10.93±3.78 μg/mL (Cp(0)), 5.93±1.18 μg/mL (Cmax)) and 6.30±0.88 μg/mL (Cmax)), respectively. Eight hours after clindamycin IV, IM and SC administration plasma concentrations declined to 2.01±0.61 μg/mL, 2.96±0.43 μg/mL and 3.36±0.97 μg/mL, respectively. Sixty to 90 minutes after clindamycin administration, tissue concentrations ranged from a minimum in subcutaneous tissue of 4.90 μg/g (IV), 3.06 μg/g (IM) and, 3.13 μg/g (SC) to a maximum in uterus of 13.41 μg/g (IV), 14.07 μg/g (IM) and, 14.44 μg/g (SC). The lowest tissue/plasma concentration ratio for the three administration routes was observed in subcutaneous tissue, while the highest was observed at genital level (ovary for IV and IM and uterus for SC). Estimated efficacy predictor (AUC/MIC), considering MIC breakpoint for bacteria isolated from animals, indicates that clindamycin administered IV, IM or SC at the studied dose is appropriated for perioperative prophylactic protocols and that given with a dose interval of 12 hours would be effective for susceptible infection treatment in cats.Facultad de Ciencias Veterinaria

Pharmacokinetics of meropenem after intravenous, intramuscular and subcutaneous administration to cats

Objectives: The aim of the study was to describe the pharmacokinetics and predicted efficacy of meropenem after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration to cats at a single dose of 10 mg/kg. Methods: Five adult healthy cats were used. Blood samples were withdrawn at predetermined times over a 12 h period. Meropenem concentrations were determined by microbiological assay. Pharmacokinetic analyses were performed with computer software. Initial estimates were determined using the residual method and refitted by non-linear regression. The time that plasma concentrations were greater than the minimum inhibitory concentration (T >MIC) was estimated by applying bibliographic MIC values and meropenem MIC breakpoint. Results: Maximum plasma concentrations of meropenem were 101.02 µg/ml (C p(0) , IV), 27.21 µg/ml (C max , IM) and 15.57 µg/ml (C max , SC). Bioavailability was 99.69% (IM) and 96.52 % (SC). Elimination half-lives for the IV, IM and SC administration were 1.35, 2.10 and 2.26 h, respectively. Conclusions and relevance: Meropenem, when administered to cats at a dose of 10 mg/kg q12h,, is effective against bacteria with MIC values of 6 μg/ml, 7 μg/ml and 10 μg/ml for IV, IM and SC administration, respectively. However, clinical trials are necessary to confirm clinical efficacy of the proposed dosage regimen.Fil: Albarellos, Gabriela Alejandra. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Montoya, Laura. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Passini, Sabrina Mariela. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Lupi, Martin Pablo. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Landoni, Maria Fabiana. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Cefuroxime plasma pharmacokinetics, tissue and urine concentrations after parenteral administration to cats

Cefuroxima es una cefalosporina de segunda generación que incluye en su espectro antibiótico a cocos gram-positivos, bacilos gram-negativos y anaerobios. El objetivo de este trabajo es caracterizar la farmacocinética plasmática de cefuroxima en gatos luego de su administración por vía intravenosa, intramuscular y subcutánea, y determinar la concentración de cefuroximaen algunos tejidos y en la orina de los animales. Luego de la administración del antibiótico (20 mg/kg), se tomaron muestras sanguíneas y de orina durante 8 horas y muestras de tejidos entre las 1-1,5 horas. Los principales parámetros farmacocinéticos (media±desvío estándar) para la administración intravenosa fueron: concentración inicial (μg/mL): 135,46±81,42; vidamedia de eliminación (h): 0,21±0,15. Para las administraciones intramuscular y subcutánea los principales parámetros farmacocinéticos fueron respectivamente: concentración máxima (μg/mL): 48,65±6,71 y 28,17±8,44, tiempo de la concentración máxima (h): 0,18±0,06 y 0,82±0,30, y vida media de eliminación (h): 1,04±0,10 y 1,59±0,18. Las concentraciones (μg/g) en tejidos estuvieron entre 3, 35±0,65 y 23.02±8.77. Al cabo de 8 horas se recuperó enla orina el 78,09±24,59% de la dosis administrada. Estos resultados indicarían que cefuroxima administrada a una dosis de 20 mg/kg por las vías estudiadas sería de utilidad para el tratamiento de infecciones producidas por microorganismos susceptibles en gatos.Cefuroxime is a second generation cephalosporin active against gram-positive cocci, gramnegative rods and anaerobes. The aim of the present study is to characterize cefuroxime plasma pharmacokinetics after intravenous, intramuscular and subcutaneous administration to cats; and, to determine cefuroxime concentrations in some tissues and in urine of the animals. After antibiotic administration (20 mg/kg), blood and urine samples were taken during 8 hours and, tissue samples at 1-1.5 hours. After intravenous administration, main pharmacokinetic parameters (mean±SD) were: initial plasma concentration (µg/mL): 135.46±81.42; half-life (h): 0.21±0.15. After intramuscular and subcutaneous administration, main pharmacokinetic parameters were, respectively: maximum plasma concentrations (µg/mL): 48.65±6.71 and 28.17±8.44; time of maximum plasma concentration were 0.18±0.06 h and 0.82±0.30 h; and, elimination half-life (h): 1.04±0.10 and 1.59±0.18. Tissue concentrations (µg/g) ranged between 3,35±0,65 and 23.02±8.77. After 8 hours, 78,09±24,59% of the administered cefuroxime was recovered from urine. The present results showed that cefuroxime, administered at a dosage of 20 mg/kg by intravenous, intramuscular or subcutaneous route, would be a useful tool for the infection treatment in cats when produced by susceptible microorganisms.Fil: Lorenzini, Paula Mercedes. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Passini, Sabrina Mariela. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Lupi, M.. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Montoya, L.. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Landoni, Maria Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Albarellos, Gabriela Alejandra. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; Argentin

Cefazolin pharmacokinetics in cats under surgical conditions

Objectives: The aim of this study was to determine the plasma pharmacokinetic profile, tissue concentrations and urine elimination of cefazolin in cats under surgical conditions after a single intravenous dose of 20 mg/kg. Methods: Intravenous cefazolin (20 mg/kg) was administered to nine young mixed-breed cats 30 mins before they underwent surgical procedures (ovariectomy or orchiectomy). After antibiotic administration, samples from blood, some tissues and urine were taken. Cefazolin concentrations were determined in all biological matrices and pharmacokinetic parameters were estimated. Results: Initial plasma concentrations were high (Cp(0), 134.80 ± 40.54 µg/ml), with fast and moderately wide distribution (distribution half-life [t½(d)] 0.16 ± 0.15 h; volume of distribution at steady state [V(d[ss])] 0.29 ± 0.10 l/kg) and rapid elimination (body clearance [ClB], 0.21 ± 0.06 l/h/kg; elimination half-life [t½], 1.18 ± 0.27 h; mean residence time 1.42 ± 0.36 h). Thirty to 60 mins after intravenous administration, cefazolin tissue concentrations ranged from 9.24 µg/ml (subcutaneous tissue) to 26.44 µg/ml (ovary). The tissue/plasma concentration ratio ranged from 0.18 (muscle) to 0.58 (ovary). Cefazolin urine concentrations were high with 84.2% of the administered dose being eliminated in the first 6 h postadministration. Conclusions and relevance: Cefazolin plasma concentrations remained above a minimum inhibitory concentration of ⩽2 µg/ml up to 4 h in all the studied cats. This suggests that a single intravenous dose of 20 mg/kg cefazolin would be adequate for perioperative prophylactic use in cats.Fil: Albarellos, Gabriela Alejandra. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Montoya, Laura. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Passini, Sabrina Mariela. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Lupi, Martin Pablo. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Lorenzini, Paula Mercedes. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Landoni, Maria Fabiana. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin