Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Apr 2013
ReviewCardiovascular disease prevention: matching evidence-based algorithms with individualized care.
The appropriate use of statins in primary prevention remains a matter of debate. Although statins reduce cardiovascular events at all levels of baseline risk, they are associated with rare but important side effects including incident diabetes. Herein, we review strategies for statin allocation ranging from strict "evidence-based" adherence to randomized controlled clinical trial (RCT) entry criteria to more "personalized" risk assessment using high-sensitivity C-reactive protein (hsCRP), coronary artery calcification (CAC), or genetic testing. Current guidelines advocate an unusual middle ground between an evidence-based approach and a personalized approach.
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Clin. Pharmacol. Ther. · Feb 2013
Practice GuidelineClinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing.
Allopurinol is the most commonly used drug for the treatment of hyperuricemia and gout. However, allopurinol is also one of the most common causes of severe cutaneous adverse reactions (SCARs), which include drug hypersensitivity syndrome, Stevens–Johnson syndrome, and toxic epidermal necrolysis. A variant allele of the human leukocyte antigen (HLA)-B, HLA-B*58:01, associates strongly with allopurinolinduced SCAR. We have summarized the evidence from the published literature and developed peer-reviewed guidelines for allopurinol use based on HLA-B genotype.
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Clin. Pharmacol. Ther. · Jan 2013
ReviewComputation as the mechanistic bridge between precision medicine and systems therapeutics.
Over the past 50 years, like molecular cell biology, medicine and pharmacology have been driven by a reductionist approach. The focus on individual genes and cellular components as disease loci and drug targets has been a necessary step in understanding the basic mechanisms underlying tissue/organ physiology and drug action. ⋯ Systems-biology approaches enable integration of knowledge from different types of data for precision medicine and systems therapeutics. In this review, we describe recent studies that contribute to these emerging fields and discuss how together these fields can lead to a mechanism-based therapy for individual patients.