RESUMEN
Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor that has shown promising results as a drug for the treatment of insulin dysregulation in horses. Even though CFZ is used clinically, no pharmacokinetic data has previously been published. In this study, the pharmacokinetics of CFZ after administration of a single oral dose of 1.8 mg/kg in eight healthy Icelandic horses was examined. Additionally, the effect of treatment on glucose and insulin levels in response to a graded glucose infusion was investigated. Plasma samples for CFZ quantification were taken at 0, 0.33, 0.66, 1, 1.33, 1.66, 2, 2.33, 2.66, 3, 3.5, 4, 5, 6, 8, 12, 24, 32, and 48 h post administration. CFZ was quantified using UHPLC coupled to tandem quadrupole mass spectrometry (UHPLC-MS/MS). A non-compartmental analysis revealed key pharmacokinetic parameters, including a median Tmax of 7 h, a Cmax of 2350 ng/mL, and a t1/2Z of 28.5 h. CFZ treatment reduced glucose (AUCGLU, p = 0.001) and insulin (AUCINS, p = 0.04) response to a graded glucose infusion administered 5 h after treatment. This indicates a rapid onset of action following a single dose in healthy Icelandic horses. No obvious adverse effects related to the treatment were observed.
RESUMEN
Bacterial cystitis is common in dogs and is usually treated with antibiotics. Nitrofurantoin is used for treatment of bacterial cystitis in humans and might provide a feasible treatment option in dogs. The aim of this study was to investigate the nitrofurantoin plasma concentration-time course and potential adverse effects in dogs. Nitrofurantoin (4.4-5.0 mg/kg) was administered orally to eight healthy beagles every 8 h for five days before repeated plasma and urine samples were collected. An additional four beagles served as untreated controls. The nitrofurantoin plasma and urine concentrations were measured using ultra high precision liquid chromatography coupled to tandem mass-spectrometry and further analysed using a non-compartmental pharmacokinetic model. In plasma, the median Cmax was 2.1 µg/mL, tmax was 2 h, the terminal rate constant was 0.9 per h and the terminal half-life was 0.8 h. In urine, median Cmax was 56 µg/mL, tmax was 1 h and the terminal half-life was 4.3 h. No adverse effects were observed clinically or in haematology or biochemistry. The data presented in this study combined with in vitro sensitivity data from common urine pathogens and the lack of observed adverse effects suggest that nitrofurantoin in a standard dosing regimen could be effective in sporadic bacterial cystitis treatment in dogs. Further clinical studies are highly warranted to verify the effectiveness in clinical cases.
Asunto(s)
Infecciones Bacterianas , Cistitis , Enfermedades de los Perros , Humanos , Perros , Animales , Nitrofurantoína/efectos adversos , Antibacterianos/efectos adversos , Antibacterianos/farmacocinética , Infecciones Bacterianas/veterinaria , Cistitis/inducido químicamente , Cistitis/tratamiento farmacológico , Cistitis/veterinaria , Plasma , Administración Oral , Semivida , Enfermedades de los Perros/tratamiento farmacológicoRESUMEN
Introduction: Atropine is an essential part of the treatment protocol for equine uveitis. Topical atropine administration has been associated with decreased intestinal motility and abdominal pain in horses. Experimental studies have indicated that frequent dosing is associated with a higher risk than dosing every 6 h. Unfortunately, no quantitative pharmacodynamic data for inhibition of the equine gut are published. Materials and methods: Eight standardbred horses were assigned to receive either atropine or saline (control) to be infused over 30 min in a two-treatment cross-over design. Atropine concentrations in plasma were measured using ultra-high-performance liquid chromatography-tandem mass spectrometry. Intestinal motility was measured using borborygmi frequency and electrointestinography (EIG). Experimental data were analyzed using a non-linear mixed effects model. The model was then used to simulate different dosing regimens. Results: Atropine significantly decreased borborygmi response and EIG response. Six horses developed clinical signs of abdominal pain. The pharmacokinetic typical values were 0.31, 1.38, 0.69, and 1.95 L/kg·h for the volumes of the central, the highly perfused, the scarcely perfused compartments, and the total body clearance, respectively. The pharmacodynamic typical values were 0.31 µg/L and 0.6 and 207 nV27 cpm for the plasma concentration at 50% of the maximum response and the maximum response and the baseline of cecal EIG response, respectively. Six different dosing regimens of topical atropine sulfate to the eye (0.4 and 1 mg every hour, every 3 h, and every 6 h) were simulated. Conclusion: The IV PK/PD data coupled with simulations predict that administration of 1 mg of topical atropine sulfate administered to the eye every hour or every 3 h will lead to atropine accumulation in plasma and decreased intestinal myoelectric activity. Administration every 6 h predicted a safe dosing regimen in full-sized horses. Clinical studies would be valuable to confirm the conclusions. For smaller equids and horses put at risk for colic due to othercauses, droplet bottles that deliver 40 µl of 1% atropine sulfate per drop or less may be used to lower the risk further.
RESUMEN
BACKGROUND: Light-emitting diodes (LEDs) are commonly used for treating a variety of disorders in horses, including wounds. Despite its claim to shorten healing times, there is a lack of scientific documentation regarding its effects. OBJECTIVES: To investigate if treatment with pulsating visible red light (λ ≈ 637 nm) and near-infrared (NIR) light (λ ≈ 956 nm) affects wound healing. STUDY DESIGN: Randomised blinded controlled experimental study. METHODS: A circular skin wound (Ø = 2 cm) was created on each side of the neck in eight healthy horses. One randomly chosen wound received light treatment and the other served as an untreated control. Treatment duration was 4 minutes and 40 seconds (red light 95 seconds, 2.3 mW/cm2 ; NIR light 185 seconds, 6.4 mW/cm2 ) and was performed once daily on day 0-4, 7-11, 14-18 and 21-25. The wounds were photographed and evaluated using digital photoplanimetry on day 0, 1, 2, 3, 4, 7, 14, 21, 28 and 35. The degree of swelling was assessed with diagnostic ultrasound on the same days except the last recording was performed on day 36 instead of 35. Days to total healing was recorded. ANOVA was used for statistical analysis (P < .05). RESULTS: The wound area (P = .2-.9) and degree of swelling (P = .2-1.0) did not differ between treated and control groups on any day. There was a significant difference (P = .03) in healing time between control (49.0, 95% CI = 35.4-62.6 days) and treated wounds (51.8, 95% CI = 38.7-64.8 days). MAIN LIMITATIONS: The wounds were treated until day 25 and this study does not investigate the effect of a longer treatment period than 25 days. CONCLUSIONS: The results of this study do not indicate any clinically relevant positive effect of pulsating visible red light and NIR light on the healing of experimental skin wounds in horses, compared with no treatment.