Exploring co-dispensed drug use in patients on sevelamer or polystyrene sulfonate to identify potential novel binding interactions: a cross sectional in silico study

Abstract BackgroundSevelamer and polystyrene sulfonate are used for treating hyperphosphatemia and hyperkalaemia in chronic kidney disease patients. Because of their binding properties, these resins potentially bind other drugs in the gastrointestinal tract, thereby decreasing their bioavailability and clinical effectiveness.AimThe aim of this study was to explore co-dispensed drug use in patients on sevelamer or polystyrene sulfonate to identify potential novel binding interactions. MethodIn this in silico study, the 100 drugs most frequently co-dispensed with sevelamer/polystyrene sulfonate in the period 2000-2018 from the University Groningen IADB.nl database were extracted. Drugs dispensed to < 5% of patients, drugs not orally administered, drugs administered once daily before bedtime and drugs for which information on binding interactions with sevelamer or polystyrene was already available were excluded. The likelihood of an interaction (yes or no) of the included drugs was assessed based on pKa- and Log P values. For sevelamer, drugs with a pKa (acid) between 1.5 and 7.4 and or a Log P value > 2.0 were identified as potential interacting drug. For polystyrene sulfonate, drugs with a pKa (base) > 1.5 were identified as potential interacting drug. ResultsOf the top 100 drugs most frequently co-dispensed with sevelamer/polystyrene sulfonate, 22 and 27 potentially clinically relevant new interacting drugs were identified for sevelamer and polystyrene sulfonate respectively. ConclusionSeveral potentially relevant novel binding interactions for sevelamer and polystyrene sulfonate were identified based on dispensing data and assessment of chemical properties for which further interaction research is warranted.

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Structural insight into the binding interactions of modeled structure of Arabidopsis thaliana urease with urea: an in silico study

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2014.915765 ◽

2014 ◽

Vol 33 (4) ◽

pp. 845-851 ◽

Cited By ~ 5

Author(s):

Vinod Kumar Yata ◽

Arun Thapa ◽

Venkata Satish Kumar Mattaparthi

Keyword(s):

Arabidopsis Thaliana ◽

In Silico ◽

Binding Interactions ◽

Modeled Structure ◽

In Silico Study ◽

Structural Insight ◽

Insight Into

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Disc measurement and nucleus calibration in a smoothened lumbar model increases the accuracy and efficiency of in-silico study

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02655-4 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Jingchi Li ◽

Chen Xu ◽

Xiaoyu Zhang ◽

Zhipeng Xi ◽

Shenglu Sun ◽

...

Keyword(s):

In Silico ◽

Area Ratio ◽

Cross Sectional Area ◽

Computational Time ◽

Sectional Area ◽

Imaging Data ◽

Cross Sectional ◽

Fea Model ◽

In Silico Study ◽

Nucleus Position

Abstract Backgrounds Finite element analysis (FEA) is an important tool during the spinal biomechanical study. Irregular surfaces in FEA models directly reconstructed based on imaging data may increase the computational burden and decrease the computational credibility. Definitions of the relative nucleus position and its cross-sectional area ratio do not conform to a uniform standard in FEA. Methods To increase the accuracy and efficiency of FEA, nucleus position and cross-sectional area ratio were measured from imaging data. A FEA model with smoothened surfaces was constructed using measured values. Nucleus position was calibrated by estimating the differences in the range of motion (RoM) between the FEA model and that of an in-vitro study. Then, the differences were re-estimated by comparing the RoM, the intradiscal pressure, the facet contact force, and the disc compression to validate the measured and calibrated indicators. The computational time in different models was also recorded to evaluate the efficiency. Results Computational results indicated that 99% of accuracy was attained when measured and calibrated indicators were set in the FEA model, with a model validation of greater than 90% attained under almost all of the loading conditions. Computational time decreased by around 70% in the fitted model with smoothened surfaces compared with that of the reconstructed model. Conclusions The computational accuracy and efficiency of in-silico study can be improved in the lumbar FEA model constructed using smoothened surfaces with measured and calibrated relative nucleus position and its cross-sectional area ratio.

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Disc Measurement and Nucleus Calibration in a Smoothened Lumbar Model Increases the Accuracy and Efficiency of in-silico Study

10.21203/rs.3.rs-521219/v1 ◽

2021 ◽

Author(s):

Jingchi Li ◽

Chen Xu ◽

Xiaoyu Zhang ◽

Zhipeng Xi ◽

Shenglu Sun ◽

...

Keyword(s):

In Silico ◽

Area Ratio ◽

Cross Sectional Area ◽

Computational Time ◽

Sectional Area ◽

Imaging Data ◽

Cross Sectional ◽

Fea Model ◽

In Silico Study ◽

Nucleus Position

Abstract Backgrounds: Finite element analysis (FEA) is an important tool during the spinal biomechanical study. Irregular surfaces in FEA models directly reconstructed based on imaging data may increase the computational burden and decrease the computational credibility. Definitions of the relative nucleus position and its cross-sectional area ratio do not conform to a uniform standard in FEA. Methods: To increase the accuracy and efficiency of FEA, nucleus position and cross-sectional area ratio were measured from imaging data. A FEA model with smoothened surfaces was constructed using measured values, nucleus position was calibrated by estimating the differences in the range of motion (RoM) between the FEA model and that of an in-vitro study. Then, the differences was re-estimated by comparing the RoM, the intradiscal pressure, the facet contact force and the disc compression to validate the measured and calibrated indicators. The computational time in different models was also recorded to evaluate the efficiency. Results: Computational results indicated that 99% of accuracy was attained when measured and calibrated indicators were set in the FEA model, with a model validation of greater than 90% attained under almost all of the loading conditions. Computational time decreased by around 70% in the fitted model with smoothened surfaces compared with that of the reconstructed model. Conclusions: The computational accuracy and efficiency of in-silico study can be guaranteed in the lumbar FEA model constructed using smoothened surfaces with measured and calibrated relative nucleus position and its cross-sectional area ratio.

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The Effect of Glargine As Basal Insulin Support for Recovering Critically Ill and High Dependency Unit Patients: An in Silico Study

7th IFAC Symposium on Modelling and Control in Biomedical Systems ◽

10.3182/20090812-3-dk-2006.00009 ◽

2009 ◽

Author(s):

Lin, Jessica

Keyword(s):

Critically Ill ◽

In Silico ◽

Basal Insulin ◽

High Dependency Unit ◽

High Dependency ◽

In Silico Study

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In Silico Study of Structural and Geometrical Requirements of Natural Sesquiterpene Lactones with Trypanocidal Activity

Mini-Reviews in Medicinal Chemistry ◽

10.2174/13895575113139990066 ◽

2013 ◽

Vol 13 (10) ◽

pp. 1407-1414 ◽

Cited By ~ 10

Author(s):

L. Fabian ◽

V. Sulsen ◽

F. Frank ◽

S. Cazorla ◽

E. Malchiodi ◽

...

Keyword(s):

In Silico ◽

Sesquiterpene Lactones ◽

Trypanocidal Activity ◽

In Silico Study

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In Silico Study of 1, 4 Alpha Glucan Branching Enzyme and Substrate Docking Studies

Current Proteomics ◽

10.2174/1570164616666190401204009 ◽

2020 ◽

Vol 17 (1) ◽

pp. 40-50

Author(s):

Farzane Kargar ◽

Amir Savardashtaki ◽

Mojtaba Mortazavi ◽

Masoud Torkzadeh Mahani ◽

Ali Mohammad Amani ◽

...

Keyword(s):

Phylogenetic Tree ◽

In Silico ◽

Alpha Helix ◽

In Silico Analysis ◽

Glycogen Storage ◽

Docking Studies ◽

Random Coil ◽

Special Topic ◽

Industrial Biotechnology ◽

In Silico Study

Background: The 1,4-alpha-glucan branching protein (GlgB) plays an important role in the glycogen biosynthesis and the deficiency in this enzyme has resulted in Glycogen storage disease and accumulation of an amylopectin-like polysaccharide. Consequently, this enzyme was considered a special topic in clinical and biotechnological research. One of the newly introduced GlgB belongs to the Neisseria sp. HMSC071A01 (Ref.Seq. WP_049335546). For in silico analysis, the 3D molecular modeling of this enzyme was conducted in the I-TASSER web server. Methods: For a better evaluation, the important characteristics of this enzyme such as functional properties, metabolic pathway and activity were investigated in the TargetP software. Additionally, the phylogenetic tree and secondary structure of this enzyme were studied by Mafft and Prabi software, respectively. Finally, the binding site properties (the maltoheptaose as substrate) were studied using the AutoDock Vina. Results: By drawing the phylogenetic tree, the closest species were the taxonomic group of Betaproteobacteria. The results showed that the structure of this enzyme had 34.45% of the alpha helix and 45.45% of the random coil. Our analysis predicted that this enzyme has a potential signal peptide in the protein sequence. Conclusion: By these analyses, a new understanding was developed related to the sequence and structure of this enzyme. Our findings can further be used in some fields of clinical and industrial biotechnology.

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Risk Minimization Measures in Off-Label Drug Use: A Survey of Community Pharmacists in Malaysia

Current Drug Safety ◽

10.2174/1573403x16666200615144946 ◽

2020 ◽

Vol 15 (3) ◽

pp. 181-189

Author(s):

Omotayo Fatokun

Keyword(s):

Informed Consent ◽

Drug Use ◽

Perceived Risk ◽

Adverse Drug Events ◽

Community Pharmacists ◽

Risk Minimization ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Off Label ◽

Written Informed Consent

Background: While off-label drug use is common and sometimes necessary, it also presents considerable risks. Therefore, measures intended to prevent or reduce the potential exposure to off-label risks have been recommended. However, little is known about community pharmacists’ beliefs regarding these measures in Malaysia. Objectives: This study examined community pharmacists’ beliefs towards risk minimization measures in off-label drug use in Malaysia and assessed the relationship between perceived risk of off-label drug use and beliefs towards risk minimization measures. Methods: A cross-sectional survey was conducted among 154 pharmacists practicing in randomly selected community pharmacies in Kuala Lumpur and the State of Selangor, Malaysia. Results: The majority agreed or strongly agreed that adverse drug events from the off-label drug should be reported to the regulatory authority (90.9%) and the off-label drug should only be used when the benefit outweighs potential risks (88.3%). Less than half (48.1%) agreed or strongly agreed that written informed consent should be obtained before dispensing off-label drugs and a majority (63.7%) agreed or strongly agreed that the informed consent process will be burdensome to healthcare professionals. Beliefs towards risk minimization measures were significantly associated with perceived risk of off-label drug use regarding efficacy (p = 0. 033), safety (p = 0.001), adverse drug rection (p = 0.001) and medication errors (p = 0.002). Conclusion: The community pharmacists have positive beliefs towards most of the risk minimization measures. However, beliefs towards written informed consent requirements are not encouraging. Enhancing risk perception may help influence positive beliefs towards risk minimization measures.

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Evaluation of Drug Use Based on WHO Prescribing Indicator in Mizan- Tepi University Teaching Hospital, south Western Ethiopia: A Cross Sectional Study

Current Drug Therapy ◽

10.2174/1574885515999200819092717 ◽

2020 ◽

Vol 15 ◽

Author(s):

Solomon Hambisa ◽

Rediet Feleke ◽

Ameha Zewudie ◽

Mohammed Yimam

Keyword(s):

Drug Use ◽

World Health Organization ◽

Teaching Hospital ◽

Cross Sectional Study ◽

University Teaching ◽

World Health ◽

Sectional Study ◽

Hospital Data ◽

Cross Sectional ◽

Health Organization

Background:: Rational drug use comprises aspects of prescribing, dispensing and patient use of medicines for different health problems. This study is aimed to assess drug prescribing practice based on the world health organization prescribing indicators in Mizan-Tepi University teaching hospital. Methods:: An institutional based retrospective cross sectional study was conducted to evaluate prescribing practices in Mizan-Tepi University teaching hospital. Data were collected based on World health organization drug use indicators using prescription papers. 600 prescriptions dispensed through the general outpatient pharmacy of the hospital were collected by systematic random sampling method from prescriptions written for a 1-year time in Mizan-Tepi University teaching hospital. Results:: The present study found that the average number of drugs per prescription was 2.04 ± 0.87 in Mizan-Tepi University teaching hospital with a range between 1 and 5. Prescribing by generic name was 97.6 % and 47.8% of prescriptions contained antibiotics in the hospital. 27.7% of prescriptions contained at least one injectable medication in Mizan-Tepi University teaching hospital. From prescribed drugs, 96.7% of them were prescribed from Ethiopian essential drug list. Conclusion:: Present study indicated that the average number of drugs prescribed per encounter, the percentage of generic prescribing and prescribing from the EDL were close to optimal value. However, the percentage of encounters with antibiotics and injections prescribed were found be very high. Thus, the study highlights some improvements in prescribing habits, particularly by focusing on the inappropriate consumption of antibiotics and injections.

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