Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Jul 2014
New oral anticoagulants vs. warfarin treatment: no need for pharmacogenomics?
For patients requiring long-term anticoagulation, oral vitamin K antagonists (VKAs) such as warfarin have overwhelming efficacy data and present significant challenges. In addition to the potential exposure to numerous drug-drug and drug-food interactions, patients receiving warfarin require frequent monitoring. It had been hoped that the integration of pharmacogenomic with clinical information would improve anticoagulation control with warfarin, but trials have not supported this aim. Novel oral anticoagulants (NOACs) offer both advantages and disadvantages and deserve consideration in appropriate patients.
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Clin. Pharmacol. Ther. · Jul 2014
ReviewHigh-density lipoproteins in the prevention of cardiovascular disease: changing the paradigm.
High-density-lipoprotein cholesterol (HDL-C) has been identified in population studies as an independent inverse predictor of cardiovascular events. Although the causal nature of this association has been questioned, HDL and its major protein, apolipoprotein (apo)A1, have been shown to prevent and reverse atherosclerosis in animal models. ⋯ However, recent clinical trials with drugs that raise HDL-C, such as niacin and inhibitors of cholesteryl ester transfer protein, have been disappointing. Here, we review the current state of the science regarding HDL as a therapeutic target.
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Clin. Pharmacol. Ther. · Jul 2014
CommentPatients benefit from genetics-guided coumarin anticoagulant therapy.
Observational studies have overwhelmingly shown that variants in the genes CYP2C9 and VKORC1 are significant determinants of individual dose of coumarin anticoagulants needed to maintain a therapeutic international normalized ratio (INR).(1) Until recently, however, few randomized clinical trials had been performed relating to the use of genetic data to predict dosing. Three sucsh clinical trials have now reported their findings.
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Clin. Pharmacol. Ther. · Jun 2014
Practice GuidelineClinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for ivacaftor therapy in the context of CFTR genotype.
Cystic fibrosis (CF) is a life-shortening disease arising as a consequence of mutations within the CFTR gene. Novel therapeutics for CF are emerging that target CF transmembrane conductance regulator protein (CFTR) defects resulting from specific CFTR variants. Ivacaftor is a drug that potentiates CFTR gating function and is specifically indicated for CF patients with a particular CFTR variant, G551D-CFTR (rs75527207). Here, we provide therapeutic recommendations for ivacaftor based on preemptive CFTR genotype results.
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Clin. Pharmacol. Ther. · May 2014
Randomized Controlled Trial Comparative StudyExposure-response relationship of T-DM1: insight into dose optimization for patients with HER2-positive metastatic breast cancer.
Exposure-response (E-R) analyses for ado-trastuzumab emtansine (T-DM1, Kadcyla) were performed using data from a randomized, active control (lapatinib plus capecitabine) trial in patients with human epidermal growth factor 2-positive metastatic breast cancer. Kaplan-Meier survival analyses stratified by T-DM1 trough concentration on day 21 of cycle 1 (Cmin,C1D21) were performed for overall survival (OS) and progression-free survival (PFS). ⋯ The percentage of patients who received T-DM1 dose adjustments was similar across the exposure range and was lower than that of the active control arm. Our findings suggest that there may be an opportunity to optimize Kadcyla dose in the patient subgroup with low T-DM1 exposure for improved efficacy with acceptable tolerability.