Annual review of pharmacology and toxicology
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Annu. Rev. Pharmacol. Toxicol. · Jan 2015
ReviewCalcitonin gene-related peptide (CGRP): a new target for migraine.
Migraine is a neurological disorder that manifests as a debilitating headache associated with altered sensory perception. The neuropeptide calcitonin gene-related peptide (CGRP) is now firmly established as a key player in migraine. Clinical trials carried out during the past decade have proved that CGRP receptor antagonists are effective for treating migraine, and antibodies to the receptor and CGRP are currently under investigation. ⋯ This review discusses mechanisms whereby CGRP enhances sensitivity to sensory input at multiple levels in both the periphery and central nervous system. Future studies on epistatic and epigenetic regulators of CGRP actions are expected to shed further light on CGRP actions in migraine. In conclusion, targeting CGRP represents an approachable therapeutic strategy for migraine.
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Annu. Rev. Pharmacol. Toxicol. · Jan 2015
ReviewDrug disposition in obesity: toward evidence-based dosing.
Obesity and morbid obesity are associated with many physiological changes affecting pharmacokinetics, such as increased blood volume, cardiac output, splanchnic blood flow, and hepatic blood flow. In obesity, drug absorption appears unaltered, although recent evidence suggests that this conclusion may be premature. ⋯ For obese children, we propose two methods to distinguish between developmental and obesity-related changes. Future research should focus on the characterization of physiological concepts to predict the optimal dose for each drug in the obese population.
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Annu. Rev. Pharmacol. Toxicol. · Jan 2015
ReviewImproving postapproval drug safety surveillance: getting better information sooner.
Adverse drug events (ADEs) are an important public health concern, accounting for 5% of all hospital admissions and two-thirds of all complications occurring shortly after hospital discharge. There are often long delays between when a drug is approved and when serious ADEs are identified. Recent and ongoing advances in drug safety surveillance include the establishment of government-sponsored networks of population databases, the use of data mining approaches, and the formal integration of diverse sources of drug safety information. These advances promise to reduce delays in identifying drug-related risks and in providing reassurance about the absence of such risks.
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Pregnant women and their fetuses are orphan populations with respect to the safety and efficacy of drugs. Physiological and absorption, distribution, metabolism, and excretion (ADME) changes during pregnancy can significantly affect drug pharmacokinetics (PK) and may necessitate dose adjustment. ⋯ By integrating physiological data, preclinical data, and clinical data (e.g., via POP-PK) to quantify anticipated changes in the PK of drugs during pregnancy, the PBPK approach allows extrapolation beyond the previously studied model drugs to other drugs with well-characterized ADME characteristics. Such a systems pharmacology approach can identify drugs whose PK may be altered during pregnancy, guide rational PK study design, and support dose adjustment for pregnant women.
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Annu. Rev. Pharmacol. Toxicol. · Jan 2013
ReviewTyrosine kinase inhibitors: views of selectivity, sensitivity, and clinical performance.
With the manufacture of imatinib, researchers introduced tyrosine kinase inhibitors (TKIs) into the clinical setting in 2000 to treat cancers; approximately fifteen other TKIs soon followed. Imatinib remains the most successful agent, whereas all the others have had modest effects on the cancers that they target. ⋯ One of the most promising approaches is to combine immune therapy with TKI treatment. In this review, the therapeutic potential of TKIs for treatment is discussed.