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Cancer patients need access to high-quality information, when making decisions about oral cancer drugs. The internet is often used as a source of information published by highly heterogeneous providers. The objective was to evaluate the quality of website providers supplying online information about oral cancer drugs. One hundred websites were analyzed using content-related and formal criteria, selected from three existing evaluation methods used for cancer websites, for medical information (defined by the German Agency for Quality in Medicine), and for the "fact box" tool. A web search by a patient was simulated to identify websites to evaluate. ANOVA was used to assess information provided by non-profit organizations (governmental and non-governmental), online newspapers, for-profit organizations, and private/unknown providers. Content-related quality differences were found between online newspapers and all other categories, with online newspapers ranking significantly lower than for-profit and non-profit websites. As for formal criteria, for-profit providers scored significantly lower than non-profit providers and online newspapers for the aspect of transparency. Internet information on oral cancer drugs published by non-profit organizations constitutes the best available web-based source of information for cancer patients. Health literacy and e-health literacy should be promoted in the public domain to allow patients to reliably apply web-based information. Certification should be required by law to ensure fulfillment of requirements for data reliability and transparency (authorship and funding) before health professionals recommend websites to cancer patients. Unfractionated heparin (UFH) dosing and monitoring guidelines for children are often extrapolated from adult data. This practice is suboptimal given the inherent differences in haemostatic maturation and drug handling in children compared with adults. The aim of this work was to investigate the impact of haemostatic system maturation on the dose-response relationship of UFH in children. A quantitative model for haemostasis in adults was adapted to account for maturation in UFH pharmacokinetic (PK) parameters with and without age-related changes in coagulation factor concentrations. The adult and adapted models were used to predict the time courses of anti-factor Xa activity (aXa) and activated partial thromboplastin time (aPTT) in patients receiving UFH infusion. Predictions from both models were compared with observed aXa and aPTT measurements from 31 paediatric patients receiving UFH during extracorporeal membrane oxygenation (ECMO). The model with maturation for both UFH PK and the haemostatic systdes a mechanistic and quantitative basis for linking physiological and pharmacological maturation to UFH effect and response biomarkers. After appropriate clinical validation, the model could be useful for the development of paediatric-specific individualised UFH dosing recommendations. Esketamine nasal spray is approved for treatment-resistant depression. The objective of this study was to characterize the pharmacokinetics of esketamine and noresketamine in healthy subjects and patients with treatment-resistant depression. Esketamine and noresketamine were measured in > 9000 plasma samples collected from 820 individuals who received esketamine by the intranasal, intravenous, and oral routes. An open linear model for esketamine (three compartments) and noresketamine (two compartments) that included a hepato-portal compartment was developed using NONMEM VII. The effects of covariates on esketamine pharmacokinetics and a model evaluation were performed using conventional methods. The fraction of a 28-mg intranasal dose absorbed through the nasal cavity (FR ) is 54% (100% of this fraction is completely absorbed); the remaining 46% is swallowed and undergoes intestinal and first-pass metabolism and 18.6% of the swallowed dose reaches the systemic circulation. https://www.selleckchem.com/products/Staurosporine.html The absolute bioavailainsic and extrinsic factors on esketamine pharmacokinetics. Clinical trials registration numbers of the studies included in the analysis ESKETINTRD1001 (NCT01780259), ESKETINTRD1002 (NCT01980303), ESKETINTRD1003 (NCT02129088), ESKETINTRD1008 (NCT02846519), ESKETINTRD1009 (NCT02343289), ESKETINTRD1010 (NCT02568176), ESKETINTRD1012 (NCT02345148), 54135419TRD1015 (NCT02682225), ESKETINTRD2003 (NCT01998958), ESKETINSUI2001 (NCT02133001), ESKETINTRD3001 (NCT02417064), ESKETINTRD3002 (NCT02418585), and ESKETINTRD3005 (NCT02422186).We aimed to review the pharmacokinetics (PK) of intravenous busulfan in paediatric patients, identify covariate factors influencing exposure, investigate evidence of changes in PK behaviour over time, and correlate exposure with efficacy and toxicity outcomes. A literature review was undertaken of original research published between 2007 and 2019, investigating the PK and pharmacodynamics (PD) of intravenous busulfan in patients ≤ 18 years of age. The review identified 41 publications characterising the PK, and 45 publications describing the PD, of busulfan. Median typical clearance (CL) was 0.22 L/h/kg and median typical volume of distribution was 0.69 L/kg. Patient weight, age, glutathione-S-transferase A1 (GSTA1) genotype and busulfan dosing day/time were the most commonly identified factors affecting CL. Of nine studies investigating changes in CL, seven reported reduced CL over the 4-day course of treatment. Exposure monitoring methods and therapeutic targets were heterogeneous across studies. Relationships between busulfan exposure and patient outcomes were observed in five studies. One study observed a cumulative area under the concentration-time curve over all days of treatment of between 78 and 101 mg/L·h, and two studies observed an average concentration at first dose of 1.88 ng/mL. Patient weight, age and GSTA1 genotype are important covariates to consider when individualising busulfan therapy. Reduced busulfan CL over time may need to be accounted for, particularly in patients not receiving phenytoin co-therapy. Standardised monitoring of busulfan exposure over the entire course of treatment and further investigation of the role of busulfan metabolites and pharmacogenomics is warranted.
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