The individual patient responses to chronic heart failure (HF) pharmacotherapies are highly variable. This variability cannot be entirely explained by clinical characteristics, and genetic variation may play a role. Therefore the purpose of this review is to 1) summarize the background pharmacogenetic literature for major HF pharmacotherapy classes (i.e. beta-blockers, angiotensin converting enzyme inhibitors, digoxin, and loop diuretics), 2) evaluate recent advances in the HF pharmacogenetic literature in the context of previous findings, and 3) discuss the challenges and conclusions for HF pharmacogenetic data and its clinical application.

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The effects of long-term hormone treatment on monoamines and monoamine metabolites in different regions of the primate brain were examined and compared. Ovariectomised Cynomologous monkeys received daily oral administration of either conjugated equine oestrogens (CEE), CEE + medroxyprogesterone acetate (MPA), or a low or high dose of tibolone, for a period of 2 years. Tissue punches collected from frozen sections through various regions of the forebrain, midbrain, and hindbrain were assayed for levels of dopamine, dihydroxyphenylacetic acid (DOPAC), serotonin, 5-hydroxyindole acetic acid (5-HIAA), and norepinephrine by high-performance liquid chromatography. Few differences between hormone-treated animals and ovariectomised controls were observed. No statistically significant effects of CEE relative to controls were detected in any of the seven brain regions analysed. Animals treated with CEE + MPA showed significant reductions in 5-HIAA in the dorsal raphe nucleus, a significant reduction in dopamine in the hypothalamus, and a significant reduction in serotonin (5-HT) levels in area 8AD of the frontal cortex. Similar to CEE, no significant effects of tibolone relative to controls were detected; however, animals treated with high-dose tibolone showed a decrease in 5-HT levels in the frontal cortex that approached significance and was similar to the effect of CEE + MPA. Collectively, the findings suggest that long-term oral administration of these compounds has relatively few effects on the levels of dopamine, serotonin, and their primary metabolites in the primate brain. This differs from the significant effects on serotonergic and dopaminergic systems detected following parenteral treatment with oestradiol and progesterone, and likely reflects differences between the effects of treating with CEE + MPA versus oestradiol and progesterone on brain monoaminergic systems.

Understanding the pharmacokinetics of drugs in peripheral body compartments, such as the genital tract, is particularly important in the infectious diseases arena. However, extracting drugs from small volumes of viscous, proteinacious substances like cervicovaginal fluid is particularly challenging. The goal of this study was to develop a method to quantify raltegravir, an HIV-1 integrase inhibitor, in the female genital tract. The method included sample preparation with perchloric acid followed by solid-phase extraction, separation with reverse-phase high-performance liquid chromatography, and detection with an ultraviolet wavelength of 218 nm. The method was linear from 0.05 to 10.0 mg/L, with minimal endogenous interference. The method was accurate (1.2-11.0% deviation) and precise (1.1-12.6% CV) for both within and between-day analyses. The ability to detect raltegravir in the female genital tract is essential for future investigations of raltegravir as an agent for prevention of HIV acquisition, and this method will be used for clinical studies further evaluating pharmacokinetic-pharmacodynamic relationships in this body compartment.

In healthy adults, a single 15-mg dose of tolvaptan administered as a crushed tablet suspended in water by NG tube resulted in AUCt and AUC∞ values that were approximately 25% lower than those observed after oral administration of a 15-mg tolvaptan tablet swallowed intact.

The antiplatelet drug clopidogrel is one of the most commonly prescribed drugs in the world, but there is wide interpatient variability in its antiplatelet effects. The majority of this variation is due to genetic effects, but there is controversy over which genetic variants are important and their relative contribution. This controversy may stem from the genetic association research paradigm, which casts the "winner's curse."

Aim To develop and apply a novel genotyping method for the 9-bp exon 1 insertion/deletion polymorphism in BDKRB2. Materials & methods DNA from 718 patients with heart failure was extracted using standard methods and a region containing exon 1 of BDKRB2 was amplified with PCR. The PCR product was separated using the Qiagen QIAxcel® capillary electrophoresis system. The bp size of the PCR product was calculated and the genotypes determined using Qiagen BioCalculator® software. Results Capillary electrophoresis accurately genotyped samples with >99% call rate and 700 s run time per row of a 96-well plate (i.e., less than 1 min per sample). The frequency of the deletion was 49% in the Caucasian patients (n = 441) and 45% in the African–American (n = 277). Conclusion Capillary electrophoresis is a rapid, accurate and sensitive method for genotyping the 9-bp exon 1 insertion/deletion polymorphism in BDKRB2.

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