Expert opinion on drug metabolism & toxicology
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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.
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Expert Opin Drug Metab Toxicol · Jun 2015
Relative contributions of the major human CYP450 to the metabolism of icotinib and its implication in prediction of drug-drug interaction between icotinib and CYP3A4 inhibitors/inducers using physiologically based pharmacokinetic modeling.
Icotinib is an anticancer drug, but relative contributions of CYP450 have not been identified. This study was carried out to identify the contribution percentage of CYP450 to icotinib and use the results to develop a physiologically based pharmacokinetic (PBPK) model, which can help to predict drug-drug interaction (DDI). ⋯ Percentage of contribution of CYP450 to icotinib metabolism was calculated by RAF. The model has been proven to fit the observed data and is used in predicting icotinib-ketoconazole/rifampin interaction.
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Expert Opin Drug Metab Toxicol · May 2015
ReviewPhysiologically based pharmacokinetic and pharmacodynamic modeling in cancer drug development: status, potential and gaps.
Modeling and simulation have become important means of answering questions relevant to the development of a drug, making it possible to assess risks early and to reduce costs. Physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) models contribute to a comprehensive understanding of the drug, covering specific questions from early discovery through lifecycle management stages. As for other disease areas, in oncology, PBPK and PD models are important topics that remain to be addressed. ⋯ PBPK/PD models have led to improvements in identifying risks and reducing costs during the drug development process. Nevertheless, there is a lot of potential, where more rigorous integration of biological knowledge and specific experimental design would result in a more comprehensive biological picture. Ideally, such approaches would reveal the extent to which preclinical work can be extrapolated to clinical settings, thus enabling reliable prediction and, ultimately, reducing failed trials in clinical oncology.
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Expert Opin Drug Metab Toxicol · Apr 2015
ReviewCangrelor for the treatment of arterial thrombosis: pharmacokinetics/pharmacodynamics and clinical data.
Dual antiplatelet therapy is the standard of care for patients with acute coronary syndromes or with recent coronary stents implantation. P2Y12 receptor antagonists have shown to reduce the risk of recurrent ischemic events among these patients, at the expense of an increased risk of bleeding. Cangrelor is a novel, intravenous, short-acting, reversible platelet P2Y12 inhibitor, which has been evaluated for the treatment of arterial thrombosis. ⋯ Cangrelor has been tested in patients with coronary artery diseases undergoing percutaneous coronary intervention and as bridging therapy for patients undergoing coronary artery bypass graft. The rapid peak of action allows a fast and complete inhibition of platelet aggregation; the rapid offset is advantageous in case of bleeding complications; and finally, the intravenous administration also makes this drug suitable for patients unable to consume oral medications. Unfortunately, the large clinical trials evaluating cangrelor in percutaneous coronary intervention did not show superiority to the standard antiplatelet therapy, and its future use in this setting still needs to be better assessed. Conversely, when used as bridging therapy to coronary artery bypass graft, cangrelor showed promising results.
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Expert Opin Drug Metab Toxicol · Apr 2015
Review Comparative StudyPharmacokinetic/pharmacodynamic evaluation of eslicarbazepine for the treatment of epilepsy.
Eslicarbazepine acetate (ESL) is a novel antiepileptic drug registered as the adjunctive treatment of partial-onset seizures in adults. As a third-generation medication, ESL is believed to have favorable efficacy/safety profile and pharmacokinetic properties in comparison with related drugs (carbamazepine and oxcarbazepine). ⋯ Results of clinical trials indicate that ESL possessed a favorable profile of anticonvulsant efficacy and tolerability as an add-on therapy in adult patients at daily doses of 800 and 1200 mg. Pediatric trials are in progress and their results will allow to characterize a role of ESL in the treatment of epilepsy in children.