The pharmacokinetics and pharmacodynamics of esomeprazole in sheep after intravenous dosing

Abomasal (gastric) ulceration is a morbidity in sheep, and currently, there is a paucity of pharmacokinetic and pharmacodynamic data for gastroprotectant drugs reported for this species. The proton pump inhibitor esomeprazole has been used in small animal and human patients for gastroprotection via increasing the gastric pH. The objective of this study was to report the pharmacokinetic parameters and pharmacodynamic effect of esomeprazole in sheep after single intravenous dosing. Four healthy adult Southdown cross ewes had blood collected over a 24  h time period after single intravenous dosing of esomeprazole at 1.0  mg/kg. Abomasal fluid was sampled over 24  h before and after esomeprazole administration. Plasma samples were analyzed for concentrations of esomeprazole and the esomeprazole metabolite, esomeprazole sulfone by high performance liquid chromatography. Pharmacokinetic and pharmacodynamic data were evaluated with specialized software. Esomeprazole was rapidly eliminated after IV administration. Elimination half-life, area under the curve, initial concentration (C0), and clearance were 0.2  h, 1,197  h*ng/mL, 4,321  ng/mL, and 0.83  mL/h/kg, respectively. For the sulfone metabolite elimination half-life, area under the curve and maximum concentration were 0.16  h, 22.5  h*ng/mL, and 65.0  ng/mL, respectively. Abomasal pH was significantly elevated from 1 to 6  h after administration and remained above 4.0 for at least 8 h after administration. No adverse effects were noted in these sheep. Esomeprazole was rapidly eliminated in sheep, similar to goats. Abomasal pH was increased, but future studies will be necessary to develop a clinical management approach to the use of esomeprazole in sheep

Pharmacokinetics of esomeprazole in goats (Capra aegagrus hircus) after intravenous and subcutaneous administration

Background: Stressed and hospitalized goats are at risk of developing abomasal (gastric) ulceration, but there is a paucity of pharmacokinetic studies for proton pump inhibiting drugs, such as, esomeprazole in goats. Objectives: The objectives for this study were to estimate plasma pharmacokinetic parameters for esomeprazole in adult goats after intravenous (IV) and subcutaneous (SQ) administration. A secondary objective was to describe the plasma kinetics of the metabolite esomeprazole sulfone after IV and SC administration in goats. Materials and methods: Esomeprazole was administered to 5 adult goats in a crossover study at doses of 1 mg/kg IV or 2 mg/kg SC. Plasma samples were collected over 36 h and analyzed via reverse phase HPLC to determine concentrations of esomeprazole and esomeprazole sulfone. Pharmacokinetic parameters were derived via non-compartmental analysis. Results: Following IV administration, mean values for plasma clearance (Cl), elimination half-life [T1/2 (λz)], C0, and volume of distribution (Vz) of esomeprazole were estimated at 24.9 mL/min/kg, 6 min, 2.324 μg/mL, and 0.23 L/kg, respectively. After SC administration elimination half-life, maximum concentration (Cmax) and time to maximum concentration (Tmax) of esomeprazole were estimated at 29 min, 1.038 μg/mL, and 22 minutes respectively. Maximum concentrations of the sulfone metabolite were 32 and 18 ng/mL after IV and SC administration. Conclusion: Esomeprazole was rapidly eliminated from plasma after both IV and SC injection in goats. The elimination half-life in goats appears to be shorter than reported in dogs, as well as less than that reported for pantoprazole in goats. The sulfone metabolite was detected and also rapidly eliminated from the plasma after both IV and SC administration. Additional pharmacodynamic investigations are needed to determine the efficacy of esomeprazole on abomasal (gastric) acid suppression in goats and could include larger doses or additional routes of administration

Use of the Extension for Community Health Outcomes (ECHO) model for public health emergency response in Alaska

ABSTRACTProject ECHO (Extension for Community Healthcare Outcomes) is a telehealth and virtual mentoring model. It is a scalable platform to create peer communities where professionals can gain knowledge, skills, and relevant information to their work and clinical practice. Key informant interviews of Alaska public health leaders, clinical providers, ECHO staff, and local government representatives were conducted to evaluate the effectiveness and utility of the Project ECHO for COVID-19 response. Project ECHO session attendance and evaluation data were also reviewed. A combined total of 41,255 attendees participated in a COVID-19 response ECHO July 1, 2019 – June 30, 2022. Eight key informant interviews were conducted with individuals involved in leading or coordinating COVID-19 response efforts. Key informants identified four themes impacting the effectiveness of the Project ECHO model in responding to the COVID-19 pandemic: (1) Engagement, (2) Amplification, (3) Adaptability, and (4) Trust. In a rapidly changing pandemic, the ECHO model provided adaptive and effective virtual spaces where Alaskan providers, communities, elected officials, educators, and other stakeholders were able to receive tailored and up-to-date information on mitigation, treatment, and other concerns exacerbated by COVID-19

Pharmacokinetics of esomeprazole in goats (Capra aegagrus hircus) after intravenous and subcutaneous administration

Background: Stressed and hospitalized goats are at risk of developing abomasal (gastric) ulceration, but there is a paucity of pharmacokinetic studies for proton pump inhibiting drugs, such as, esomeprazole in goats. Objectives: The objectives for this study were to estimate plasma pharmacokinetic parameters for esomeprazole in adult goats after intravenous (IV) and subcutaneous (SQ) administration. A secondary objective was to describe the plasma kinetics of the metabolite esomeprazole sulfone after IV and SC administration in goats. Materials and methods: Esomeprazole was administered to 5 adult goats in a crossover study at doses of 1 mg/kg IV or 2 mg/kg SC. Plasma samples were collected over 36 h and analyzed via reverse phase HPLC to determine concentrations of esomeprazole and esomeprazole sulfone. Pharmacokinetic parameters were derived via non-compartmental analysis. Results: Following IV administration, mean values for plasma clearance (Cl), elimination half-life [T1/2 (λz)], C0, and volume of distribution (Vz) of esomeprazole were estimated at 24.9 mL/min/kg, 6 min, 2.324 μg/mL, and 0.23 L/kg, respectively. After SC administration elimination half-life, maximum concentration (Cmax) and time to maximum concentration (Tmax) of esomeprazole were estimated at 29 min, 1.038 μg/mL, and 22 minutes respectively. Maximum concentrations of the sulfone metabolite were 32 and 18 ng/mL after IV and SC administration. Conclusion: Esomeprazole was rapidly eliminated from plasma after both IV and SC injection in goats. The elimination half-life in goats appears to be shorter than reported in dogs, as well as less than that reported for pantoprazole in goats. The sulfone metabolite was detected and also rapidly eliminated from the plasma after both IV and SC administration. Additional pharmacodynamic investigations are needed to determine the efficacy of esomeprazole on abomasal (gastric) acid suppression in goats and could include larger doses or additional routes of administration.This article is published as Fladung R, Smith JS, Hines MT, Soto-Gonzalez WM, Fayne B, Rahn RR, Escher OG, Harvill L, Bergman J, Garcia JD, Kreuder AJ and Cox S (2022) Pharmacokinetics of esomeprazole in goats (Capra aegagrus hircus) after intravenous and subcutaneous administration. Front. Vet. Sci. 9:968973. DOI: 10.3389/fvets.2022.968973. Copyright 2022 Fladung, Smith, Hines, Soto-Gonzalez, Fayne, Rahn, Escher, Harvill, Bergman, Garcia, Kreuder and Cox. Attribution 4.0 International (CC BY 4.0). Posted with permission

Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo