Expert opinion on drug metabolism & toxicology
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Expert Opin Drug Metab Toxicol · Sep 2016
ReviewAcute, transitional and long-term cluster headache treatment: pharmacokinetic issues.
The cornerstones of cluster headache therapy are based on the tripod of acute, transitional and preventative treatments that respectively aim to the control of the bouts, the transitional suppression of the relapse and the prevention of the entire cluster period. Particularly in chronic cluster headache, where a long-term preventative therapy is necessary, multiple drug regimens increase the risk of drug-drug interactions leading to variability in the clinical efficacy and to potentially harmful adverse effects. ⋯ Pharmacokinetic interactions for both preventive, transitional and acute drugs are significant with a number of xenobiotics and other medications. Therefore, the pharmacokinetic issues knowledge is advisable for a safe and effective cluster headache management.
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Expert Opin Drug Metab Toxicol · Sep 2016
ReviewOpioids in the treatment of restless legs syndrome: pharmacological and clinical aspects.
Restless legs syndrome (RLS) is a common neurologic sensory-motor disorder that can have a negative impact on sleep, quality of life and health. In patients affected by severe RLS, pharmacological treatment is mandatory. ⋯ The drugs currently available for the treatment of RLS do not always allow to obtain an optimal control of symptoms, in particular, when utilised for long-term treatment. Opioids as monotherapy or add-on treatment should be considered when alternative satisfactory regimens are unavailable and the severity of symptoms warrants it. In a phase III trial oxycodone-naloxone prolonged-release (PR) demonstrated a significant and sustained effect on patients with severe RLS inadequately controlled by previous treatment. It was recently approved for the second-line symptomatic treatment of severe to very severe idiopathic RLS, after failure of dopaminergic treatment. Further studies are needed to evaluate if oxycodone-naloxone PR is equally efficacious as a first-line treatment. Moreover, long-term comparative studies between opioids, dopaminergic drugs and α-2-δ ligands are needed.
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Expert Opin Drug Metab Toxicol · Sep 2016
ReviewPharmacokinetics, pharmacodynamics and clinical efficacy of nivolumab in the treatment of metastatic renal cell carcinoma.
Nivolumab is a recombinant, humanized monoclonal antibody that binds PD-1. The binding of PD-1 with PD-L1, expressed on antigen-presenting cells and tumor cells, suppresses the ability of T-lymphocytes to recognize and destroy tumor cells. Nivolumab reverts this inhibitory signal and has led to a significant prolongation of overall survival in patients with metastatic renal cell carcinoma (RCC). ⋯ Nivolumab demonstrated a statistically significant advantage over everolimus in overall survival in metastatic RCC patients after first-line antiangiogenic therapy. Nevertheless, a number of issues remain to be resolved regarding the use of this drug in RCC. It is now imperative to identify which patients can benefit most from immunotherapy and studies are ongoing to define its role in other settings and/or in combinations with antiCTLA4 or antiangiogenic drugs.