scholarly journals Excellent Clinical and Pharmacokinetic Real-World Experience after Switching to Rurioctocog ALFA Pegol

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 26-27
Author(s):  
Olga Benitez Hidalgo ◽  
Francisco Jose Lopez Jaime ◽  
María Fernanda Martínez García ◽  
Juan Carlos Juarez Gimenez ◽  
Eva Alvarez Martinez ◽  
...  
Keyword(s):  
Half Life ◽  
Area Under The Curve ◽  
Previous Treatment ◽  
Life Time ◽  
Coagulation Factors ◽  
Bleeding Events ◽  
Bleeding Rate ◽  
Entire Cohort ◽  
Therapeutic Alternative ◽  
Weekly Infusion

Background:Prophylactic treatment with standard half-life coagulation factors (SHL) requires 3-4 weekly periodic infusions. Extended half-life (EHL) factor VIII (FVIII) provides improvements in half-life (t1/2) and area under the curve (AUC) of 1.3 and 1.25 times compared to standard half-life (SHL) products. Rurioctocog alfa pegol is an extended half-life (EHL) rFVIII (rFVIII-EHL) treatment that could be a more convenient and cost-effective therapeutic alternative than SHL, since it would reduce the number of weekly infusions (NWI). Aims:The aim of this study is to analyze pharmacokinetic (PK) parameters and compare NWI and bleeding rates after switching from SHL to this EHL in hemophilia A (HA) patients. Methods:In a prospective study, the number of weekly infusions (NWI), annualized bleeding rate (ABR), annualized joint bleeding rate (AJBR), and PK parameters were compared between previous treatment with FVIII-SHL vs rFVIII-EHL (Rurioctocog alfa pegol). The assessment of the PK parameters: volume of distribution (Vd (dL/kg)), clearance (Cl (dL/h/kg)) and half-life time (t½ (h)) was performed by using the pharmacokinetic poblacional software online myPKFiT®. Results:Nineteen patients from 2 Spanish hospitals (n=12 Vall d'Hebron Hospital, n=7 Hospital Regional Universitario de Málaga) were recruited. Median age was 30 years (range, 12-54), with five pediatric patients, and 18 had severe HA (one moderate HA). Sixteen patients were under prophylactic treatment with Advate® and 1 with Kovaltry®. Two patients were switched from on-demand treatment to prophylaxis. The median use of rFVIII-EHL was 15.63 month. The PK parameters after the switch to the rFVIII-EHL in entire cohort and pediatric cohort are shown in Table 1. The t ½ of rFVIII-EHL was positively correlated to preinfusion plasma levels of von Willebrand factor antigen (vWF:Ag) (Figure 1). ABR and AJBR were reduced, as well as weekly infusion frequency (33.3%, IQR:0-50%) (Table 2). Of note, 57.9% of patients presented zero joint bleeding events after switchingtorFVIII-EHL. Conclusions:In this prospective analysis rFVIII- EHL presents as a therapeutic alternative that allows reducing ABR and AJBR as well as weekly infusion frequency according to PK patient parameters. Disclosures Bosch: Roche:Honoraria;Celgene:Honoraria;Jansen:Honoraria;Abbvie:Honoraria;Novartis:Honoraria;Astra Zeneca:Honoraria;Takeda:Honoraria.Gironella Mesa:Bristol Myers Squibb:Honoraria, Speakers Bureau;Janssen:Consultancy, Honoraria.

Covalent Complexes Between Low Molecular Weight Heparin Fragments and Antithrombin III – Inhibition Kinetics and Turnover Parameters

1983 ◽  
Vol 49 (02) ◽  
pp. 109-115 ◽  
Author(s):  
M Hoylaerts ◽  
E Holmer ◽  
M de Mol ◽  
D Collen
Keyword(s):  
Molecular Weight ◽  
Half Life ◽  
Low Molecular Weight Heparin ◽  
Antithrombin Iii ◽  
Factor Xa ◽  
Life Time ◽  
Low Molecular Weight ◽  
High Affinity ◽  
Plasma Half Life ◽  
Covalent Complex

SummaryTwo high affinity heparin fragments (A/r 4,300 and M, 3,200) were covalently coupled to antithrombin III (J. Biol. Chem. 1982; 257: 3401-3408) with an apparent 1:1 stoichiometry and a 30-35% yield.The purified covalent complexes inhibited factor Xa with second order rate constants very similar to those obtained for antithrombin III saturated with these heparin fragments and to that obtained for the covalent complex between antithrombin III and native high affinity heparin.The disappearance rates from plasma in rabbits of both low molecular weight heparin fragments and their complexes could adequately be represented by two-compartment mammillary models. The plasma half-life (t'/j) of both low Afr-heparin fragments was approximately 2.4 hr. Covalent coupling of the fragments to antithrombin III increased this half-life about 3.5 fold (t1/2 ≃ 7.7 hr), approaching that of free antithrombin III (t1/2 ≃ 11 ± 0.4 hr) and resulting in a 30fold longer life time of factor Xa inhibitory activity in plasma as compared to that of free intact heparin (t1/2 ≃ 0.25 ± 0.04 hr).

Simultaneous optimization of activity and stability of xylose reductase from D. nepalensis NCYC 3413 using statistical experimental design

2020 ◽  
Vol 27 ◽  
Author(s):  
Shwethashree Malla ◽  
Sathyanarayana N. Gummadi
Keyword(s):  
Half Life ◽  
Specific Activity ◽  
Enzyme Stability ◽  
Reductase Activity ◽  
Xylose Reductase ◽  
Life Time ◽  
Economic Feasibility ◽  
Simultaneous Optimization ◽  
Physical Parameters ◽  
Statistical Experimental Design

Background: Physical parameters like pH and temperature play a major role in the design of an industrial enzymatic process. Enzyme stability and activity are greatly influenced by these parameters; hence optimization and control of these parameters becomes a key point in determining the economic feasibility of the process. Objective: This study was taken up with the objective to optimize physical parameters for maximum stability and activity of xylose reductase from D. nepalensis NCYC 3413 through separate and simultaneous optimization studies and comparison thereof. Method: Effects of pH and temperature on the activity and stability of xylose reductase from Debaryomyces nepalensis NCYC 3413 were investigated by enzyme assays and independent variables were optimised using surface response methodology. Enzyme activity and stability were optimised separately and concurrently to decipher the appropriate conditions. Results: Optimized conditions of pH and temperature for xylose reductase activity were determined to be 7.1 and 27 ℃ respectively, with predicted responses of specific activity (72.3 U/mg) and half-life time (566 min). The experimental values (specific activity 50.2 U/mg, half-life time 818 min) were on par with predicted values indicating the significance of the model. Conclusion: Simultaneous optimization of xylose reductase activity and stability using statistical methods is effective as compared to optimisation of the parameters separately.

Radical Intermediates in Photochemical and Redox Initiated Decomposition of Thioazo Compounds(an EPR and Cyclovoltammetric Study)

1997 ◽  
Vol 62 (6) ◽  
pp. 855-865 ◽  
Author(s):  
Katarína Erentová ◽  
Vladimír Adamčík ◽  
Andrej Staško ◽  
Oskar Nuyken ◽  
Arming Lang ◽  
...  
Keyword(s):  
Decomposition Rate ◽  
Half Life ◽  
Spin Trap ◽  
Solvent Molecule ◽  
Life Time ◽  
Radical Intermediates ◽  
Reactive Radicals ◽  
Induced Decomposition

The cathodically and photochemically induced decomposition of thioazo compounds XC6H4-N2-S-C6H4CH3 and their polymers with X = NO2, COOH, and SO3H were investigated. The formation of carbon-centered XC6H4. and sulfur-centered .S-C6H4Y radicals was confirmed using spin-trap technique. These reactive radicals either abstract hydrogen from CH3CN solvent molecule forming .CH2CN radical or they recombine to cage products XC6H4-S-C6H4CH3 eliminating N2. The decomposition rate of the investigated thioazo compounds is characterized by a formal half-life time of 5 to 10 s.

scholarly journals Observational study of thrombosis and bleeding in COVID-19 VV ECMO patients

2021 ◽  
pp. 039139882198906
Author(s):  
Brianda Ripoll ◽  
Antonio Rubino ◽  
Martin Besser ◽  
Chinmay Patvardhan ◽  
William Thomas ◽  
...  
Keyword(s):  
Intensive Care ◽  
Ct Scan ◽  
Thrombotic Event ◽  
Area Under The Curve ◽  
Whole Body ◽  
Bleeding Events ◽  
Heparin Resistance ◽  
Increased Risk ◽  
Thrombotic Complications ◽  
Clinically Significant

Introduction: COVID-19 has been associated with increased risk of thrombosis, heparin resistance and coagulopathy in critically ill patients admitted to intensive care. We report the incidence of thrombotic and bleeding events in a single center cohort of 30 consecutive patients with COVID-19 supported by veno-venous extracorporeal oxygenation (ECMO) and who had a whole body Computed Tomography Scanner (CT) on admission. Methodology: All patients were initially admitted to other hospitals and later assessed and retrieved by our ECMO team. ECMO was initiated in the referral center and all patients admitted through our CT scan before settling in our intensive care unit. Clinical management was guided by our institutional ECMO guidelines, established since 2011 and applied to at least 40 patients every year. Results: We diagnosed a thrombotic event in 13 patients on the initial CT scan. Two of these 13 patients subsequently developed further thrombotic complications. Five of those 13 patients had a subsequent clinically significant major bleeding. In addition, two patients presented with isolated intracranial bleeds. Of the 11 patients who did not have baseline thrombotic events, one had a subsequent oropharyngeal hemorrhage. When analyzed by ROC analysis, the area under the curve for % time in intended anticoagulation range did not predict thrombosis or bleeding during the ECMO run (0.36 (95% CI 0.10–0.62); and 0.51 (95% CI 0.25–0.78); respectively). Conclusion: We observed a high prevalence of VTE and a significant number of hemorrhages in these severely ill patients with COVID-19 requiring veno-venous ECMO support.

Acute coronary syndrome patients with two minor high-bleeding risk criteria have the same bleeding rate that patients with one major criteria

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Cordero ◽  
J.M Garcia-Acuna ◽  
M Rodriguez-Manero ◽  
B Cid ◽  
B Alvarez Alvarez ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Academic Research ◽  
Bleeding Risk ◽  
Bleeding Events ◽  
Post Discharge ◽  
Bleeding Rate ◽  
Coronary Syndrome ◽  
All Cause Mortality ◽  
High Bleeding Risk ◽  
Minor Criteria

Abstract Background In 2019 the Academic Research Consortium of high-bleeding risk (ARC-HBR) proposed a new and binary definition of high-bleeding risk (HBR) patients based on the presence of 1 major or 2 minor criteria. Methods Prospective study of all consecutive patients admitted for ACS in two different centers. We analyzed bleeding incidence in patients with 1 major criteria (1MC) vs. 2 minor criteria (2mC) using the 2019 ARC-HBR consensus. Bleeding events were collected according those fitting definitions 3 or 5 of the BARC consortium. Results We included 8,724 patients included and 40.9% we classified as HBR; 20.9% for 1MC and 20.0% for 2mC. In-hospital mayor bleeding rate was 8.6%; no-HBR patients had 0.3%, 2mC 15.1% and 1MC 29.7% (p<0.001 for the comparison). In contrast, the statistically highest in-hospital mortality was observed in patients with 2mC (11.4%), followed by patients with 1MC (8.0%) and no-HBR patients (2.0%). During follow-up (median time 57.8 months) all-cause mortality rate was 21.0% and cardiovascular dead 14.2%. The incidence of post-discharge major bleeding was 10.5%. No-HBR patients had the lowest bleeding rate (7.4%) and no difference was observed in patients with 1MC (14.6%) or 2mC (15.8%) (figure). The multivariate analysis, adjusted by age, gender, medical treatment, atrial fibrillation and revascularization and considering all-cause mortality as competing risk, showed independent association of 1MC (sHR: 1.46, 95% 1.22–1.75) and 2mC (sHR: 1.31, 95% CI 1.05–1.63) with post-discharge major bleeding. Conclusions HBR patients according to the 2019 ARC-HBR containing 2mC or 1MC are at similar and higher risk of in-hospital or post-discharge bleeding events Funding Acknowledgement Type of funding source: None

scholarly journals Grasses and legumes as cover crop in no-tillage system in northeastern Pará Brazil

2014 ◽  
Vol 44 (4) ◽  
pp. 411-418 ◽  
Author(s):  
Renato Alves Teixeira ◽  
Tatiana Gazel Soares ◽  
Antonio Rodrigues Fernandes ◽  
Anderson Martins de Souza Braz
Keyword(s):  
Half Life ◽  
Dry Matter ◽  
C:N Ratio ◽  
Life Time ◽  
Dry Matter Production ◽  
Agricultural Systems ◽  
Climate Conditions ◽  
Jack Bean ◽  
No Till ◽  
Matter Production

Studies to select one or more species of coverage plants adapted to Amazonian soil and climate conditions of the Amazon are a promising strategy for the improvement of environmental quality, establishing no-till agricultural systems, and thereby reducing the impacts of monoculture farming. The aim of this study was to assess the persistence time, half-life time, macronutrient content and accumulation, and C:N ratio of straw coverage in a Ultisol in northeastern Pará. Experimental design was randomized blocks with five treatments and five replicates. Plants were harvested after 105 days, growth and biomass production was quantified. After 84 days, soil coverage was 97, 85, 52, 50, and 15% for signalgrass (Brachiaria brizantha) (syn. Urochloa), dense crowngrass (Panicum purpurascens), jack bean (Canavalia ensiformes), pearl millet (Pennisetum americanum) and sunn hemp (Crotalaria juncea,), respectively. Signalgrass yielded the greatest dry matter production (9,696 kg ha-1). It also had high C:N ratio (38.4), long half-life (86.5 days) and a high persistence in the field. Jack bean also showed high dry matter production (8,950 kg ha-1), but it had low C:N ratio (17.4) and lower half-life time (39 days) than the grasses. These attributes indicate that signalgrass and jack bean have a high potential for use as cover plants in no-till agricultural systems in the State of Pará.

Prophylaxis for Hemophilia in the Era of Extended Half-Life Factor VIII/Factor IX Products

2016 ◽  
Vol 42 (05) ◽  
pp. 518-525 ◽  
Author(s):  
Erik Berntorp ◽  
Nadine Andersson
Keyword(s):  
Half Life ◽  
Safety Margin ◽  
Clinical Development ◽  
Factor Ix ◽  
Life Extension ◽  
Bleeding Events ◽  
Treatment And Prevention ◽  
Trough Levels ◽  
Life Factor

There are two main bioengineering approaches to extending the half-life of factor (F)VIII or FIX products used for hemophilia replacement therapy. These are fusion to Fc-immunoglobulin G (FVIII and FIX) or to albumin (FIX) or pegylation/glycopegylation (FVIII and FIX). Four FVIII and three FIX products are in clinical development or have recently been licensed in regions of the world. The reported half-life extension is approximately 1.5-fold for FVIII and 2.5-fold, or even longer, for FIX. Clinical trials have shown promising results with respect to extension of dose intervals and efficacy in the treatment and prevention of bleeding events. The role of these products in clinical practice has been discussed in terms of either improving convenience and adherence through prolongation of the interval between infusions or maintaining current intervals thereby increasing trough levels and the safety margin against bleeds. This review of extended half-life products addresses the possibilities and problems of their introduction in hemophilia treatment.

Abstract P277: Impact of Fructose and Fructose Containing Sugars on Indices of Cardiometabolic Health When Consumed at Typical Levels

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Joshua Lowndes ◽  
Stephanie Sinnett ◽  
Kory Grench ◽  
Richard Jordan ◽  
James Rippe
Keyword(s):  
Caloric Intake ◽  
Area Under The Curve ◽  
Heart Association ◽  
Normal Diet ◽  
Cardiometabolic Health ◽  
Random Group ◽  
Added Sugars ◽  
Entire Cohort ◽  
Group Assignment ◽  
The One

The American Heart Association recommends that women and men should not consume more than 100 or 150 kcal/day, respectively, from added sugars. Pure fructose in large dosages has been shown to adversely affect indices of cardiometabolic health in a variety of ways. However, pure fructose is rarely consumed, and it is unclear whether the same risks apply to the common sources of fructose in the American diet - sucrose and high fructose corn syrup (HFCS). The purpose of this study was to compare the effect on components of cardiometabolic health of fructose compared to other fructose containing sugars and glucose when consumed at levels typical of the American population. 268 individuals aged 20-60 years old were required to drink sugar-sweetened low fat milk every day for 10 weeks as part of their usual diet. All participants had been at a stable weight (± 3%) for 30 days prior to enrollment and were given recommendations on how to account for calories in the milk, but were given no further dietary guidance. The amount of milk consumed was individualized for each participant based on the estimated number of calories required to maintain body weight (via Miflin St Jeor equation) and random group assignment: Groups 1 and 2 - 9% estimated caloric intake from fructose or glucose respectively added to milk. Groups 3 and 4 - 18% of estimated caloric intake from HFCS or sucrose respectively added to the milk (50 th percentile population consumption levels of fructose, 180-360 Kcal). There was a small increase in body mass (162.2 ± 27.8 vs 164.2 ± 28.1 lbs, p<0.001) in the entire cohort, but there were no changes in HDL (52.51 ±12.77 vs 52.36 ± 12.40 mg/dl), CRP (1.63 ±1.77 vs 176 ±1.94 mg/L), fasting glucose (90 ± 6.50 vs 90.66 ±7.89 mg/dl), insulin (8.55 ±6.10 vs 11.20 ±39.32 (μIU/ml), HOMA measurement of insulin resistance (1.60 ±1.43 vs 1.74 ±1.29), or the glucose (13.28 ±2.53 vs 13.16 ±2.56 min*mg/dl) or insulin (2.52 ±1.32 vs 2.54 ± 1.57 min*mU/ml) area under the curve in response to an OGTT (all p>0.05). Small increases in waist circumference (80.88 ±9.45 vs 81.45 ± 9.46cm, p<0.001), abdominal fat measured by DEXA (36.31 ± 11.58 vs 36.84 ± 11.20% p<0.05), and Apolipoprotein B (86.53 ±25.79 vs 90.78 vs 25.62 mg/dl, p<0.001) were observed, but in all cases the type of sugar consumed had no effect on the response of any measure (p>0.05). The one exception was triglycerides, which increased in the entire cohort (101.56 ± 56.47 vs 111.70 vs 79.14mg/dl, p<0.01), but to a greater degree in the group consuming HFCS than compared to the group consuming glucose (98.20 ± 52.46 vs 129.03 ± 120.49 and 100.28 ±56.19 vs 99.86 ± 57.21mg/dl, p<0.05). These data suggest that when consumed as part of normal diet at typical levels the effects of sugars on cardiovascular risk factors are small and primarily limited to aspects of body composition even when levels are substantially higher than those recommended by the AHA.

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