Inflammation is an evolutionary process that allows survival against acute infection or injury. Inflammation is also a pathophysiological condition shared by numerous chronic diseases. In addition, inflammation modulates important drug-metabolizing enzymes and transporters (DMETs), thus contributing to intra- and interindividual variability of drug exposure. A better knowledge of the impact of inflammation on drug metabolism and its related clinical consequences would help to personalize drug treatment. Here, we summarize the kinetics of inflammatory mediators and the underlying transcriptional and post-transcriptional mechanisms by which they contribute to the inhibition of important DMETs. We also present an updated overview of the effect of inflammation on the pharmacokinetic parameters of most of the drugs that are DMET substrates, for which therapeutic drug monitoring is recommended. Furthermore, we provide opinions on how to integrate the inflammatory status into pharmacogenetics, therapeutic drug monitoring, and population pharmacokinetic strategies to improve the personalization of drug treatment for each patient.

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Purpose Sharing and developing digital educational resources and open educational resources has been proposed as a way to harmonize and improve clinical pharmacology and therapeutics (CPT) education in European medical schools. Previous research, however, has shown that there are barriers to the adoption and implementation of open educational resources. The aim of this study was to determine perceived opportunities and barriers to the use and creation of open educational resources among European CPT teachers and possible solutions for these barriers. Methods CPT teachers of British and EU medical schools completed an online survey. Opportunities and challenges were identified by thematic analyses and subsequently discussed in an international consensus meeting. Results Data from 99 CPT teachers from 95 medical schools were analysed. Thirty teachers (30.3%) shared or collaboratively produced digital educational resources. All teachers foresaw opportunities in the more active use of open educational resources, including improving the quality of their teaching. The challenges reported were language barriers, local differences, lack of time, technological issues, difficulties with quality management, and copyright restrictions. Practical solutions for these challenges were discussed and include a peer review system, clear indexing, and use of copyright licenses that permit adaptation of resources. Conclusion Key challenges to making greater use of CPT open educational resources are a limited applicability of such resources due to language and local differences and quality concerns. These challenges may be resolved by relatively simple measures, such as allowing adaptation and translation of resources and a peer review system.

Taxanes are anticancer drugs on the market for more than 10 years that are thought to be interesting for therapeutic drug monitoring (TDM): high inter- and intra-patient variability, relationship between exposure and efficacy and especially toxicity. Nevertheless, the paclitaxel and docetaxel characteristics result in different conclusions for these two molecules with respect to their TDM. For paclitaxel, the nonlinear pharmacokinetics makes that the parameter which seems the more reliable to toxicity or outcome is the time during which the plasma concentration exceeds 0.05 μm. Concentration controlled studies using Bayesian adaptation showed that the TDM of paclitaxel is feasible in routine. However, this target needs to be prospectively validated with new weekly schedules of administration, leading to a balance between 'recommended' and 'potentially useful'. For docetaxel, the 3-weekly administration, which is the more effective scheme, is also the more toxic. However, neutropenia can be individually modeled and efficiently predicted without using plasma drug concentrations. The docetaxel TDM using this docetaxel-related neutropenia modeling however needs to be prospectively validated in routine. The level of evidence of TDM thus 'needs to be assessed'.

Glaser NS, Geller DH, Haqq A, Gitelman S, Malloy M. Detecting and treating hyperlipidemia in children with type 1 diabetes mellitus: are standard guidelines applicable to this special population?

Although traditional approaches to biomarker discovery have elucidated key molecular markers that have improved drug selection (precision medicine), the discovery of biomarkers that inform optimal dose selection (precision dosing) continues to be a challenge in many therapeutic areas. Larger and more diverse study populations are necessary to discover additional biomarkers that provide the resolution needed for a more tailored dose. To generate and accommodate large datasets of drug response phenotypes, time‐ and cost‐efficient strategies are necessary. In particular, a multitude of technological advances that originated for purposes outside of biomedical research (electronic health records, direct‐to‐consumer genetic testing, social media, mobile devices, and machine learning) have made it easier to communicate, connect, and gather information from consumers. Although these technologies have been used with success in the health sciences for an array of purposes, these resources have not been fully capitalized on for precision dosing. This perspective will touch on how these innovations can be used as data sources, data collection tools, and data processing tools for drug‐response phenotypes with a unique focus on advancing biomarker‐driven precision dosing.

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Oral etoposide displays high intervariability and intravariability. Convincing relationships were observed between hematological toxicities and exposure of which total etoposide area under the curve seems the more relevant in routine practice. Linear pharmacokinetics, limited sampling strategies and reduction in variability during concentration-controlled studies argue in favor of therapeutic drug monitoring. However, such reduction in variability should be confirmed after oral administration. For these reasons, such practice can be considered as 'potentially useful'. Further studies using Bayesian approach are nevertheless needed to definitely state regarding the level of evidence therapeutic drug monitoring of oral etoposide.