Pharmacokinetics and pharmacodynamics of intravenous and oral apixaban in horses.

Large vessel and microvascular thrombi are common complications in systemically ill horses contributing to patient morbidity and mortality. Apixaban, an oral factor Xa inhibitor, shows excellent efficacy against stroke and deep vein thrombosis in humans. The purpose of this study was to determine serum apixaban concentrations and anti-factor Xa activity in horses after orally administered apixaban. Five horses received a single dose of intravenous (0.09 mg/kg) and oral (1 mg/kg) apixaban in a cross-over design. Serum apixaban concentrations and anti-Xa activity were measured serially via liquid chromatography-tandem mass spectrometry and a commercial assay, respectively, for 12 hr following oral administration. Apixaban was detected in all horses after both oral and intravenous administration. Oral administration yielded a mean maximum concentration of 60.3 ng/ml (59.4-111 ng/ml), mean time to maximum concentration of 0.5 hr (0.5-2), mean half-life of 6.2 hr (4.6-8.3), and mean oral bioavailability of 10% (3.8-17.4). After oral administration, anti-Xa activity had a strong positive relationship with serum apixaban and was best represented by a dose-response model with the following parameters: E0  = 5.00 ng/ml, EMAX  = 311 ng/mL, EC50  = 267 ng/ml, and n = 1.58. Anti-Xa activity was significantly higher 2 hr post-administration compared with baseline (p = .032). Despite low oral bioavailability, administration of 1 mg/kg oral apixaban, in healthy horses, achieves serum concentrations similar to those reported in humans. Apixaban has potential clinical utility in horses and warrants further investigation.

Urine sodium concentration after intravenous furosemide in dogs with acute congestive heart failure and correlation with treatment efficacy.

BACKGROUND: Poor natriuresis is a potential marker of diuretic resistance in dogs with acute congestive heart failure (CHF) but little is known about the relationship between urine sodium concentration (uNa) and frequency of successful decongestion. Supplemental O2 is a common treatment in dogs with severe CHF. The time from start to discontinuation of supplemental O2 therapy (DCSO2 ) typically reflects the time course and ease of decongestion. HYPOTHESIS/OBJECTIVES: Urine Na concentration after IV administration of furosemide will be correlated with duration of treatment with supplemental O2 (timeO2 ) and the cumulative frequency of successful DCSO2 during hospitalization. ANIMALS: Fifty-one dogs with acute CHF. METHODS: Retrospective observational single center study. RESULTS: Dogs with low uNa had significantly longer mean timeO2 than dogs with high uNa (uNa <87 mmol/L, 24.2 ± 2.6 hours vs uNa ≥87 mmol/L, 16.6 ± 1.7 hours; P = .02). Low uNa was correlated with lower cumulative frequency of DCSO2 (12 hour, 28%; 24 hour, 42%; 36 hour, 73%) compared to high uNa (12 hour, 28%; 24 hour, 88%; 36 hour, 96%; P = .005). History of PO loop diuretics, low serum chloride concentration (sCl), and high PCV were associated with low uNa. Urine Na concentration outperformed other metrics of diuretic responsiveness including weight loss. CONCLUSIONS AND CLINICAL IMPORTANCE: Urine Na concentration after IV furosemide predicted timeO2 and cumulative frequency of DCSO2 in dogs with acute CHF, which likely reflects important aspects of diuretic responsiveness. Urine Na can assess diuretic responsiveness and treatment efficacy in dogs with CHF.

Utility of focused cardiac ultrasonography training in veterinary students to differentiate stages of subclinical myxomatous mitral valve disease in dogs.

BACKGROUND: Differentiation of the subclinical phases of myxomatous mitral valve disease (MMVD) in dogs relies heavily on echocardiography. Focused cardiac ultrasonography (FCU) is a point-of-care technique that can assess heart size. HYPOTHESIS/OBJECTIVES: Veterinary students trained in FCU can differentiate dogs with subclinical MMVD based on left ventricular (LV) and left atrial (LA) dimensions. ANIMALS: Forty-eight dogs with subclinical MMVD. METHODS: Veterinary students were trained to measure LV dimension and LA-to-aortic root dimension ratio (LA : Ao) using FCU. Dogs were categorized into 2 cohorts based on whether or not the LV normalized internal diastolic dimension was ≥1.7 and LA : Ao was ≥1.6. Agreement between FCU and echocardiographic studies performed by cardiologists was evaluated. RESULTS: One-hundred and forty-six FCU examinations were performed by 58 veterinary students on 48 dogs. Overall agreement between students and cardiologists was moderate (Fleiss' kappa, 0.54; 95% confidence interval [CI], 0.39-0.69; P < .001). Percentage accuracy in observations with heart dimensions less than the cutoffs (86/89, 97%) was significantly higher than in observations in with larger hearts (31/57, 54%; P < .001). Agreement increased from moderate to good as heart sizes became more extreme. Degree of confidence by students in performing FCU was significantly higher at the end vs start of the study. CONCLUSIONS AND CLINICAL IMPORTANCE: Categorization of dogs with subclinical MMVD by veterinary students using FCU was associated with moderate to good agreement with echocardiography. Focused cardiac ultrasonography is a point-of-care method that can help assess clinical stage in dogs with subclinical MMVD.