RESUMO
Sulfamethoxazole-trimethoprim (SMZ-TMP), a commonly prescribed antibiotic for backyard hens, is neither Food and Drug Administration approved nor prohibited in laying hens in the United States. The aim of this study was to determine whether plasma concentrations above targeted minimum inhibitory concentration breakpoint values for Enterobacteriaceae could be achieved with oral dosing. Five Rhode Island red hens (Gallus gallus domesticus) were administered a single dose of 96 mg/kg SMZ-TMP (80 mg/kg SMZ and 16 mg/kg TMP) IV followed by the same dose orally after a washout period. Following oral dosing, mean SMZ concentrations exceeded the target breakpoint for approximately 12 hours; however, TMP only briefly exceeded the target breakpoint. Bioavailability was 60.5% for SMZ and 82.0% for TMP. Ten naïve birds were allocated into control (n = 4) and treatment (n = 6) groups for a 7-day multi-dose study. Treatment birds received an oral suspension dosed at 16 mg/kg TMP and 80 mg/kg SMZ every 48 hours (on days 1, 3, 5, and 7); TMP tablets were additionally dosed at 25 mg/bird on days 1, 3, 5, and 7, and 50 mg/bird on days 2, 4, and 6. Plasma SMZ-TMP concentrations were measured on a multiple time interval by ultraperformance liquid chromatography-mass spectrometry, and pharmacokinetic analyses were performed using a noncompartmental model. No accumulation for either drug was noted following repeated dosing, and no statistical differences in biochemical values, packed cell volumes, or weight were found between pre- and posttreatment in either the treatment or control groups. Sulfamethoxazole (80 mg/kg q48h PO) and TMP (24.1-28.0 mg/kg q24h PO) maintained therapeutic plasma concentrations at or exceeding the minimum inhibitory concentration breakpoint of Enterobacteriaceae for 72 and 24 hours for TMP and SMZ, respectively, without evidence of adverse effects or drug accumulation. Further studies are needed to refine this dosage regimen and evaluate adverse effects in ill birds.
Assuntos
Galinhas , Combinação Trimetoprima e Sulfametoxazol , Animais , Feminino , Rhode Island , Combinação de Medicamentos , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Administração OralRESUMO
OBJECTIVE: Sporadic bacterial cystitis in both dogs and humans is often caused by Escherichia coli. In humans, nitrofurantoin is a first-line antimicrobial for the treatment of bacterial cystitis but in dogs a lack of available data may be part of the reason it is only recommended as a second-line treatment. The objective of this preliminary study was to determine the plasma pharmacokinetics and urine concentrations of nitrofurantoin monohydrate-macrocrystalline in dogs. ANIMALS: 8 healthy female hound dogs. PROCEDURES: From July 26 to July 28, 2021, dogs received a single oral dose of nitrofurantoin monohydrate-macrocrystalline 100 mg with food. Blood and urine were collected at predetermined times. Nitrofurantoin concentrations were assayed by UPLC-MS/MS and plasma data were analyzed using noncompartmental methods. RESULTS: Plasma concentrations were low for all dogs with a mean ± SD maximum concentration (Cmax) of 0.242 ± 0.098 µg/mL (range, 0.14 to 0.42 µg/mL) occurring between 2 and 24 hours. Urine concentrations were manyfold higher than for plasma. Cmax in urine was 134 ± 54 µg/mL (range, 49.1 to 218 µg/mL) occurring between 6 and 36 hours. As seen in other species, nitrofurantoin concentrated in urine with concentrations being 500 times higher than the concentration in plasma. CLINICAL RELEVANCE: Results suggested that nitrofurantoin monohydrate-macrocrystalline formulation of nitrofurantoin should be effective in treating bacterial cystitis caused by susceptible uropathogens.