Expert opinion on drug metabolism & toxicology
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Expert Opin Drug Metab Toxicol · Jul 2015
ReviewNeonatal medicines research: challenges and opportunities.
The key feature of the newborn is its fast age-dependent maturation, resulting in extensive variability in pharmacokinetics and -dynamics, further aggravated by newly emerging covariates like treatment modalities, environmental issues or pharmacogenetics. This makes clinical research in neonates relevant and needed, but also challenging. ⋯ Challenges relating to neonatal medicine research can largely be overcome. Tailored tools and legal initiatives, combined with clever trial design will result in more robust information on neonatal pharmacotherapy. This necessitates collaborative efforts between clinical researchers, sponsors, regulatory authorities, and last but not least patient representatives and society.
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Expert Opin Drug Metab Toxicol · Jul 2015
ReviewTools for predicting the PK/PD of therapeutic proteins.
Assessments of the pharmacokinetic/pharmacodynamic (PK/PD) characteristics are an integral part in the development of novel therapeutic agents. Compared with traditional small molecule drugs, therapeutic proteins possess many distinct PK/PD features that necessitate the application of modified or separate approaches for assessing their PK/PD relationships. ⋯ A variety of state-of-the-art PK/PD tools is currently being applied and has been adjusted to support the development of proteins as therapeutics, including allometric scaling approaches, target-mediated disposition models, first-in-man dose calculations, physiologically based PK models and empirical and semi-mechanistic PK/PD modeling. With the advent of the next generation of biologics including bioengineered antibody constructs being developed, these tools will need to be further refined and adapted to ensure their applicability and successful facilitation of the drug development process for these novel scaffolds.
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Expert Opin Drug Metab Toxicol · Jul 2015
ReviewMedication overuse and chronic migraine: a critical review according to clinical pharmacology.
Chronic migraine is often complicated by medication-overuse headache (MOH), a headache due to excessive intake of acute medications. Chronic migraine and MOH are serious and disabling disorders. Since chronic migraine derives from the progression of originally episodic migraine, the fundamental therapeutic strategy is prevention. This narrative review describes how to try to prevent the development of MOH and how to manage it once it has appeared. ⋯ In spite of progress in migraine treatment, the prevalence of chronic headaches and MOH has not changed in the course of time. Today, a large number of migraine patients have turned to numerous expert physicians and experienced all sorts of prophylactic treatments without decisive benefits. Their condition seems to have crystallized even more as chronic and intractable. This means that to prevent chronification and MOH, we need more effective drugs and better strategies to use them. In particular, we must detect disease biomarkers and predictive factors for drug response that allow for personalized treatment when migraine is still episodic and make analgesic overuse pointless.