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Ring, Arne; Schall, Robert; Loke, Yoon K.; Day, Simon
doi: 10.1111/bcp.13254pmid: 28321897
Research in clinical pharmacology covers a wide range of experiments, trials and investigations: clinical trials, systematic reviews and meta‐analyses of drug usage after market approval, the investigation of pharmacokinetic–pharmacodynamic relationships, the search for mechanisms of action or for potential signals for efficacy and safety using biomarkers. Often these investigations are exploratory in nature, which has implications for the way the data should be analysed and presented. Here we summarize some of the statistical issues that are of particular importance in clinical pharmacology research.
Lee, Hannah H.; Ho, Richard H.
doi: 10.1111/bcp.13207pmid: 27936281
OATP1B1 (SLCO1B1) is predominantly expressed at the basolateral membrane of hepatocytes and is critically important for the hepatic uptake and clearance of numerous drug substrates and endogenous compounds. In general, the organic anion transporting polypeptides (OATP; SLCO) represent a superfamily of uptake transporters that mediate the sodium‐independent transport of a diverse range of amphipathic organic compounds including bile salts, steroid conjugates, thyroid hormones, anionic peptides, numerous drugs and other xenobiotic substances. OATP1B1 is highly polymorphic and a number of relevant and ethnically dependent polymorphisms have been identified and functionally characterized. In particular, the SLCO1B1 521T>C and 388A>G polymorphisms are commonly occurring variants in ethnically diverse populations and numerous in vitro and clinical studies have evaluated the consequences of these variants to interindividual differences in drug disposition and response. OATP1B1 is particularly important for the disposition of HMG‐CoA reductase inhibitors, or statins, as it is known to efficiently transport most statins to their site of action within hepatocytes. Many studies have focused on the consequences of OATP1B1 variants to statin disposition in vitro and in vivo and would suggest that genetic variability in SLCO1B1 has important implications for statin pharmacokinetics, risk for statin‐induced myopathy, and modulation of statin treatment response. This review describes what is currently known regarding SLCO1B1 genotype, OATP1B1 protein expression and interindividual and interethnic consequences to drug disposition, with particular focus on statin pharmacokinetics and implications for drug response and toxicity.
Chan, Bosco; Reeve, Emily; Matthews, Slade; Carroll, Peter R.; Long, Janet C.; Held, Fabian; Latt, Mark; Naganathan, Vasi; Caplan, Gideon A.; Hilmer, Sarah N.
doi: 10.1111/bcp.13222pmid: 28009444
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