scholarly journals Pharmacokinetic/Pharmacodynamic Considerations of Alternate Dosing Strategies of Tocilizumab in COVID-19

2021 ◽  
Author(s):  
Elizabeth Leung ◽  
Ryan L. Crass ◽  
Sarah C. J. Jorgensen ◽  
Sumit Raybardhan ◽  
Bradley J. Langford ◽  
...  
Keyword(s):  
Dosing Strategies

scholarly journals Veno-venous ECMO as a platform to evaluate lung lavage and surfactant replacement therapy in an animal model of severe ARDS

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Robert Qaqish ◽  
Yui Watanabe ◽  
Marcos Galasso ◽  
Cara Summers ◽  
A adil Ali ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Lung Lavage ◽  
Post Injury ◽  
Surfactant Replacement ◽  
Recruitment Maneuvers ◽  
Surfactant Replacement Therapy ◽  
Dosing Strategies ◽  
Yorkshire Pigs ◽  
Saline Lavage ◽  
Protective Systems

Abstract Background There are limited therapeutic options directed at the underlying pathological processes in acute respiratory distress syndrome (ARDS). Experimental therapeutic strategies have targeted the protective systems that become deranged in ARDS such as surfactant. Although results of surfactant replacement therapy (SRT) in ARDS have been mixed, questions remain incompletely answered regarding timing and dosing strategies of surfactant. Furthermore, there are only few truly clinically relevant ARDS models in the literature. The primary aim of our study was to create a clinically relevant, reproducible model of severe ARDS requiring extracorporeal membrane oxygenation (ECMO). Secondly, we sought to use this model as a platform to evaluate a bronchoscopic intervention that involved saline lavage and SRT. Methods Yorkshire pigs were tracheostomized and cannulated for veno-venous ECMO support, then subsequently given lung injury using gastric juice via bronchoscopy. Animals were randomized post-injury to either receive bronchoscopic saline lavage combined with SRT and recruitment maneuvers (treatment, n = 5) or recruitment maneuvers alone (control, n = 5) during ECMO. Results PaO2/FiO2 after aspiration injury was 62.6 ± 8 mmHg and 60.9 ± 9.6 mmHg in the control and treatment group, respectively (p = 0.95) satisfying criteria for severe ARDS. ECMO reversed the severe hypoxemia. After treatment with saline lavage and SRT during ECMO, lung physiologic and hemodynamic parameters were not significantly different between treatment and controls. Conclusions A clinically relevant severe ARDS pig model requiring ECMO was established. Bronchoscopic saline lavage and SRT during ECMO did not provide a significant physiologic benefit compared to controls.

scholarly journals Evaluation of Direct Oral Anticoagulant Prescribing in Patients With Moderate to Severe Renal Impairment

2021 ◽  
Vol 27 ◽  
pp. 107602962098790
Author(s):  
Clara Ting ◽  
Megan Rhoten ◽  
Jillian Dempsey ◽  
Hunter Nichols ◽  
John Fanikos ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Impairment ◽  
Severe Renal Impairment ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Events ◽  
Increase Risk ◽  
Severe Chronic Kidney Disease ◽  
Dosing Strategies ◽  
Require Dose

Patients with renal impairment require dose adjustments for direct oral anticoagulants (DOACs), though there is uncertainty regarding their use in severe chronic kidney disease. Inappropriately dosed DOACs may increase risk of ischemic events when under-dosed, or risk of bleeding when over-dosed. The purpose of this study was to describe DOAC selection, dosing strategies, and associated clinical outcomes in patients with moderate to severe renal impairment at our institution. This was a single-center retrospective analysis of adult outpatients with moderate to severe renal impairment (estimated creatinine clearance <50 mL/min, including need for hemodialysis) who were prescribed a DOAC by a cardiologist between June 1, 2015 and December 1, 2018. Outcomes evaluated included the percentage of patients who received appropriate and inappropriate DOAC dosing, prescriber reasons for inappropriate DOAC dosing if documented, and incidence of thrombotic and bleeding events. A total of 207 patients were included. Overall, 61 (29.5%) patients received inappropriate dosing, with 43 (70.5%) being under-dosed and 18 (29.5%) being over-dosed as compared to FDA-labeled dosing recommendations for atrial fibrillation or venous thromboembolism (VTE). By a median follow-up duration of 20 months, stroke occurred in 6 (3.3%) patients receiving DOACs for atrial fibrillation, and VTE occurred in 1 (4.3%) patient receiving a DOAC for VTE. International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding occurred in 25 (12.1%) patients. Direct oral anticoagulants were frequently prescribed at off-label doses in patients with moderate to severe renal impairment, with a tendency toward under-dosing.

Paclitaxel Pharmacokinetics, Threshold Models, and Dosing Strategies

2003 ◽  
Vol 21 (14) ◽  
pp. 2803-2804 ◽  
Author(s):  
Alex Sparreboom ◽  
Jaap Verweij
Keyword(s):  
Threshold Models ◽  
Dosing Strategies

Dosing Strategies for Antiplatelet Therapy in Percutaneous Coronary Intervention

2010 ◽  
Vol 38 (2) ◽  
pp. 50-58 ◽  
Author(s):  
Gilles Lemesle ◽  
Gabriel Maluenda ◽  
Laurent Bonello ◽  
Cédric Delhaye ◽  
Arnaud Sudre ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Antiplatelet Therapy ◽  
Coronary Intervention ◽  
Percutaneous Coronary ◽  
Dosing Strategies

A Control-Theoretic Approach to Neural Pharmacology: Optimizing Drug Selection and Dosing

2016 ◽  
Vol 138 (8) ◽  
Author(s):  
Gautam Kumar ◽  
Seul Ah Kim ◽  
ShiNung Ching
Keyword(s):  
Design Method ◽  
Target Space ◽  
Theoretic Approach ◽  
Time Varying ◽  
Drug Selection ◽  
Modeling Paradigm ◽  
Dosing Strategies ◽  
Dose Dependent ◽  
Optimal Construction ◽  
Selection Of

The induction of particular brain dynamics via neural pharmacology involves the selection of particular agonists from among a class of candidate drugs and the dosing of the selected drugs according to a temporal schedule. Such a problem is made nontrivial due to the array of synergistic drugs available to practitioners whose use, in some cases, may risk the creation of dose-dependent effects that significantly deviate from the desired outcome. Here, we develop an expanded pharmacodynamic (PD) modeling paradigm and show how it can facilitate optimal construction of pharmacologic regimens, i.e., drug selection and dose schedules. The key feature of the design method is the explicit dynamical-system based modeling of how a drug binds to its molecular targets. In this framework, a particular combination of drugs creates a time-varying trajectory in a multidimensional molecular/receptor target space, subsets of which correspond to different behavioral phenotypes. By embedding this model in optimal control theory, we show how qualitatively different dosing strategies can be synthesized depending on the particular objective function considered.

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