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1.
J Vet Pharmacol Ther ; 43(3): 297-302, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32157713

RESUMEN

Cefuroxime axetil pharmacokinetic profile was investigated in 12 Beagle dogs after single intravenous and oral administration of tablets or suspension at a dose of 20 mg/kg, under both fasting and fed conditions. A three-period, three-treatment crossover study (IV, PO under fasting and fed condition) was applied. Blood samples were withdrawn at predetermined times over a 12-hr period. Cefuroxime plasma concentrations were determined by HPLC. Data were analyzed by compartmental analysis. No statistically significant differences were observed between formulations and feeding conditions on PK parameters. Independently of the feeding condition, absorption of cefuroxime axetil after tablet administration was low and erratic. The drug has been quantified in plasma in 3 out of 6 and 5 out of 6 dogs in the fasted and fed groups. For this formulation, the bioavailability (F), peak plasma concentration (Cmax ), and area under the concentration-time curve (AUC) of cefuroxime axetil were significantly enhanced (p < .05) by the concomitant ingestion of food (32.97 ± 13.47-14.08 ± 7.79%, 6.30 ± 2.62-2.74 ± 0.66 µg/ml, and 15.75 ± 3.98-7.82 ± 2.76 µg.hr/ml for F, Cmax, and AUC in fed and fasted dogs, respectively), while for cefuroxime axetil suspension, feeding conditions affected only the rate of absorption, as reflected by the significantly shorter absorption half-life (T½(a) ) and time to peak concentration (Tmax ) (0.55 ± 0.27-1.15 ± 0.19 hr and 1.21 ± 0.22-1.70 ± 0.30 for T½(a) and Tmax in fed and fasted dogs, respectively). For cefuroxime axetil tablets, T > MIC (≤1 µg/ml) was <2 hr in fasted and ≈4 hr in fed animals, and for cefuroxime axetil suspension, T > MIC (≤1 µg/ml) was ≈5 hr and for T >MIC (≤4 µg/ml) was ≈2.5 hr for fasted and fed dogs, respectively. Cefuroxime axetil as a suspension formulation seems to be a better option than tablets. However, its short permanence in plasma could reduce its clinical usefulness in dogs.


Asunto(s)
Antibacterianos/farmacocinética , Cefuroxima/análogos & derivados , Perros/sangre , Interacciones Alimento-Droga , Administración Intravenosa , Administración Oral , Animales , Área Bajo la Curva , Cefuroxima/farmacocinética , Perros/metabolismo , Femenino , Semivida , Masculino
2.
J Feline Med Surg ; 19(10): 992-997, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27609113

RESUMEN

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.


Asunto(s)
Gatos/metabolismo , Gatos/cirugía , Cefazolina/farmacocinética , Orquiectomía/veterinaria , Ovariectomía/veterinaria , Animales , Gatos/sangre , Cefazolina/administración & dosificación , Cefazolina/sangre , Femenino , Semivida , Infusiones Intravenosas , Masculino , Distribución Tisular
3.
J Feline Med Surg ; 18(12): 976-980, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-26347549

RESUMEN

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 (Cp(0), IV), 27.21 µg/ml (Cmax, IM) and 15.57 µg/ml (Cmax, 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.


Asunto(s)
Antibacterianos/farmacocinética , Gatos/metabolismo , Tienamicinas/farmacocinética , Animales , Antibacterianos/administración & dosificación , Área Bajo la Curva , Disponibilidad Biológica , Femenino , Semivida , Inyecciones Intramusculares/veterinaria , Inyecciones Intravenosas/veterinaria , Inyecciones Subcutáneas/veterinaria , Meropenem , Pruebas de Sensibilidad Microbiana , Tienamicinas/administración & dosificación
4.
J Feline Med Surg ; 15(6): 483-7, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23253883

RESUMEN

The study describes the pharmacokinetics and predicted efficacy of imipenem after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration to five adult cats at a dose of 5 mg/kg. Susceptibility to imipenem [minimum inhibitory concentration (MIC)] was determined for antimicrobial resistant Escherichia coli (n = 13) and staphylococci (n = 3) isolated from domestic cat infections (urinary system, skin and conjunctiva). Maximum plasma concentrations of imipenem were 13.45 µg/ml (IV), 6.47 µg/ml (IM) and 3.83 µg/ml (SC). Bioavailability was 93.18% (IM) and 107.90% (SC). Elimination half-lives for IV, IM and SC administration were 1.17, 1.44 and 1.55 h, respectively. All tested bacteria were susceptible to imipenem; MIC values were 0.03 µg/ml for Staphylococcus species and <0.25-0.5 µg/ml for E coli. Mean imipenem concentrations remained above a MIC of 0.5 µg/ml for approximately 4 h (IV and IM) and 9 h (SC). Imipenem would be predicted to be effective for the treatment of antimicrobial resistant bacterial infections in cats at a dosage of 5 mg/kg every 6-8 h (IV, IM), or longer for the SC route. However, clinical trials are mandatory to establish its efficacy and proper dosing.


Asunto(s)
Antibacterianos/farmacocinética , Gatos/sangre , Imipenem/farmacocinética , Animales , Antibacterianos/administración & dosificación , Antibacterianos/sangre , Disponibilidad Biológica , Cilastatina/administración & dosificación , Combinación Cilastatina e Imipenem , Estudios Cruzados , Combinación de Medicamentos , Farmacorresistencia Bacteriana , Escherichia coli/efectos de los fármacos , Femenino , Semivida , Imipenem/administración & dosificación , Imipenem/sangre , Inyecciones Intramusculares , Inyecciones Intravenosas , Inyecciones Subcutáneas , Masculino , Staphylococcus/efectos de los fármacos
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