Expert review of clinical pharmacology
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Expert Rev Clin Pharmacol · Jul 2019
ReviewAlternatives to antibiotics in an era of difficult-to-treat resistance: new insights.
Introduction: The rise of antibiotic resistance, the limited efficacy and the adverse events associated with antibiotics have urged the development of alternative measures to treat bacterial infections. Novel therapies which are pathogen specific and are safer to the healthy microbiome are being developed. Areas covered: This manuscript provides a compact overview of the feasibility and clinical impact of the latest novel therapies, with a focus on monoclonal antibodies (mAbs), vaccines, stem cells, bacteriophages, and liposomes. ⋯ Stem cells and bacteriophages still have a long way to go. Vaccines are always desirable to prevent infections but again there is a lack of confirmatory results. Broad spectrum liposomes have shown promising results in treating severely infected patients and could be game changers in patient management.
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Expert Rev Clin Pharmacol · Jun 2019
ReviewClinical pharmacology of caplacizumab for the treatment of patients with acquired thrombotic thrombocytopenic purpura.
Introduction: Caplacizumab is a humanized anti-von Willebrand Factor (vWF) Nanobody® for the treatment of acquired Thrombotic Thrombocytopenic Purpura (aTTP). Caplacizumab targets the A1-domain of vWF, inhibiting the interaction between vWF and platelets. Clinical studies conducted in aTTP patients confirmed the rapid and sustained complete suppression of the vWF activity using an initial intravenous dose of 10 mg, and a maintenance subcutaneous 10 mg daily dosing regimen, with corresponding favorable efficacy and safety profiles. ⋯ Renal and hepatic impairment are not expected to influence the exposure to the drug, and no direct or indirect drug-drug pharmacokinetic interactions are anticipated based on the mechanism of action and the specificity of the pharmacodynamic effect of caplacizumab. Expert opinion: Caplacizumab prevents the interaction between vWF and platelets, offering a direct and rapid therapeutic intervention to stop microthrombosis. The combination of caplacizumab with plasma exchange and immunosuppression represents an important, potentially life-saving advance in the treatment of aTTP patients.
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Introduction: Advanced cancers that did not respond to chemotherapy were once a death sentence, but now there are newer therapies utilizing the patient's own immune system to fight cancer that are proving effective in chemotherapy-refractory malignancies. However, this success against cancer cells may be accompanied by immune-related adverse events that can affect the kidneys. Areas covered: Using Medline and Scopus, we compiled all publications through February 2019 that pertained to immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor T-cells (CAR T-cells). The focus of this review is the discussion of these new cancer therapies, with attention to the reported kidney-related adverse effects.. ⋯ These self-protective mechanisms have been appropriated by tumor cells as a means of evading immune detection and destruction. New immunotherapies such as immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy incite an aggressive immune response directed against tumor cells. This unrestrained activation of the immune system may result in kidney injury via multiple mechanisms.
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Expert Rev Clin Pharmacol · Mar 2019
Review Comparative StudyEncorafenib in combination with binimetinib for unresectable or metastatic melanoma with BRAF mutations.
Combination treatment with a BRAF inhibitor and MEK inhibitor is the standard of care for patients with advanced BRAFV600 mutation-positive melanoma. With the currently available combinations of dabrafenib plus trametinib and vemurafenib plus cobimetinib, median progression-free survival (PFS) of over 12 months has been achieved. However, treatment resistance and disease recurrence remain a clinical challenge. ⋯ This improved efficacy may be related to the distinct pharmacokinetics of encorafenib, with prolonged binding to the target molecule providing greater BRAF inhibition and increased potency compared with other drugs in the same class. Increased specificity of encorafenib may also result in better tolerability with less off-target effects, including reduced occurrence of pyrexia and photosensitivity. Encorafenib plus binimetinib seems likely to emerge as a valuable therapeutic alternative to established BRAF/MEK inhibitor combinations.
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Expert Rev Clin Pharmacol · Mar 2019
ReviewLorlatinib for the treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer.
Approximately 3-5% of patients with non-small cell lung cancer (NSCLC)belonged to anaplastic lymphoma kinase (ALK)-positive NSCLC. The treatment drugs of ALK-positive NSCLC mainly included crizotinib, ceritinib, alectinib, and brigatinib. Although these drugs had some effects, most of them were usually easy to develop drug resistance. ⋯ Lorlatinib could also pass through the blood-brain barrier, which had a good effect on patients with brain metastasis. Adverse events of lorlatinib were mostly mild and moderate in severity, and patients were easily tolerated. Most common adverse events were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea.