Therapeutic drug monitoring
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Over the last couple of decades, molecular diagnostics have played an increasing role in drug development. Especially within oncology, more and more drugs are being developed together with a predictive biomarker assay using the drug-diagnostic codevelopment model. Not only do these assays support the development process but also the use of the drugs after regulatory approval as an important treatment decision tool. ⋯ However, only for pembrolizumab, the PD-L1 immunohistochemical (IHC) 22C3 pharmDx assay has status as a companion diagnostic. For nivolumab and atezolizumab, the assays PD-L1 IHC 22C3 pharmDx and Ventana PD-L1 (SP142) have status as complementary diagnostics, which means that there are no requirements for testing included in the labeling for these drugs. Here, the authors discuss the clinical performance of the different IHC PD-L1 expression assays including the selection of the clinical cutoff values.
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New psychoactive substances (NPSs) are substitutes for classical drugs of abuse and there are now compounds available from all groups of classical drugs of abuse. During 2014, the number of synthetic cathinones increased dramatically and, together with phenylethylamines, they dominate the NPS markets in the European Union. In total, 31 cathinones and 9 phenylethylamines were encountered in 2014. The aim of this article was to summarize the existing knowledge about the basic pharmacology, metabolism, and human toxicology of relevant synthetic cathinones and phenylethylamines. Compared with existing reviews, we have also compiled the existing case reports from both fatal and nonfatal intoxications. ⋯ The acute and chronic toxicity of many NPSs is unknown or very sparsely investigated. There is a need for evidence-based-treatment recommendations for acute intoxications and a demand for new strategies to analyze these compounds in clinical and forensic cases.
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Review
AUC versus peak-trough dosing of vancomycin: applying new pharmacokinetic paradigms to an old drug.
To compare and contrast the pharmacokinetic/pharmacodynamic foundations of traditional "peak-trough" vancomycin dosing methods versus newer "area under the curve" (AUC) strategies. To propose a new AUC-based dosing chart for empirically determining an initial vancomycin dosing regimen designed to achieve a desired AUC24 using the minimum inhibitory concentration (MIC), creatinine clearance (CrCl), and vancomycin clearance (ClVanco). ⋯ An understanding of pharmacokinetic and pharmacodynamic principles, including the relevance of AUC in relation to MIC, enables clinicians to make the best use of vancomycin dosing options. The proposed dosing chart is pharmacokinetically valid but has yet to be applied clinically. It provides a foundation for further study of how clinicians can determine an optimal AUC-based starting vancomycin dosing regimen without having to derive ClVanco or AUC24.
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Codeine is an old and commonly used analgesic agent for mild to moderate pain. It is the prototypical "prodrug" in that its analgesic effect is almost wholly dependent on its biotransformation to morphine, a process that is mediated by the polymorphic cytochrome P450 2D6 enzyme. ⋯ This review will discuss the relative role of pharmacogenetics and therapeutic drug monitoring in predicting and/or maintaining adequate and safe analgesia with codeine. The review will end on a discussion of how the marriage of these 2 fields may provide new insights into the mechanisms of codeine-induced toxicity and analgesia.
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Although risperidone is commonly used in the acute and maintenance treatment of schizophrenia, the role of therapeutic drug monitoring has yet to be elucidated. The purpose of this review was to determine whether risperidone warrants therapeutic drug monitoring in patients with schizophrenia. ⋯ The routine use of risperidone levels does not seem warranted in all patients with schizophrenia. Clinical end points (ie, response and toxicity) should be monitored by assessing changes in symptoms and emergence of adverse effects, especially extrapyramidal symptoms. Therapeutic drug monitoring of risperidone may be beneficial in certain circumstances, including assessing potential noncompliance and supporting compliance, ruling out therapeutic failure as a result of low drug concentrations, and identifying and managing drug interactions, adverse effects, and use in special populations.