Urine concentrations of vilanterol and its metabolites, GSK932009 and GW630200, after inhalation of therapeutic and supratherapeutic doses.

The 2023 Prohibited List issued by the World Anti-Doping Agency (WADA) permits athletes to inhale the beta -agonist vilanterol at a standard dose of 25 μg daily. However, given limited data on urine pharmacokinetics, vilanterol has no urinary threshold or decision limit to discriminate therapeutic from supratherapeutic use. We investigated urine concentrations of vilanterol and its main metabolites GSK932009 and GW630200 over 0-72 h following inhalation of therapeutic (25 μg) or supratherapeutic (100 μg) doses and repeat-dose administration for 7 days of 25 or 100 μg·day in 25 trained men and women.

Assay validation for vilanterol and its metabolites in human urine with application for doping control analysis.

A bioanalytical method for detecting the ultra-long-acting beta -agonist (U-LABA) inhaled vilanterol and its metabolites, GSK932009 and GW630200, in urine was developed to potentially monitor permitted therapeutic versus prohibited supratherapeutic use in sport. The World Anti-Doping Agency (WADA) has established urinary concentration thresholds for the beta -agonists salbutamol and formoterol. Therapeutic use of vilanterol (25 μg once daily) was recently permitted by WADA; however, there is no established decision limit for adverse analytical findings due to insufficient urine concentration data.

The Extent and Impact of Variation in ADME Genes in Sub-Saharan African Populations.

Investigating variation in genes involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs are key to characterizing pharmacogenomic (PGx) relationships. ADME gene variation is relatively well characterized in European and Asian populations, but data from African populations are under-studied-which has implications for drug safety and effective use in Africa. We identified significant ADME gene variation in African populations using data from 458 high-coverage whole genome sequences, 412 of which are novel, and from previously available African sequences from the 1,000 Genomes Project.

The safety, tolerability, and pharmacokinetic profile of GSK2838232, a novel 2nd generation HIV maturation inhibitor, as assessed in healthy subjects.

This work aimed to assess the safety, tolerability, pharmacokinetics (PK), and relative bioavailability of GSK2838232, an investigational HIV maturation inhibitor. GSK2838232 was administered over four dose-escalation studies in healthy subjects which assessed single oral doses (5-250 mg) and repeat doses (up to 200 mg once or twice daily) ±100 mg ritonavir (RTV) once daily. GSK2838232 administration (up to 250 mg) to 124 subjects across four studies resulted in few mild adverse events (AEs) with similar frequencies to placebo.

Pharmacokinetics, pharmacodynamics and adverse event profile of GSK2256294, a novel soluble epoxide hydrolase inhibitor.

Aims: Endothelial-derived epoxyeicosatrienoic acids may regulate vascular tone and are metabolized by soluble epoxide hydrolase enzymes (sEH). GSK2256294 is a potent and selective sEH inhibitor that was tested in two phase I studies.

Methods: Single escalating doses of GSK2256294 2-20 mg or placebo were administered in a randomized crossover design to healthy male subjects or obese smokers.

Substantial nitrous oxide emissions from intertidal sediments and groundwater in anthropogenically-impacted West Falmouth Harbor, Massachusetts.

Large N2O emissions were observed from intertidal sediments in a coastal estuary, West Falmouth Harbor, MA, USA. Average N2O emission rates from 41 chambers during summer 2008 were 10.7 mol N2O m(-2) h(-1)±4.

Cytochrome P450 gene induction in rats ex vivo assessed by quantitative real-time reverse transcriptase-polymerase chain reaction (TaqMan).

Drug-induced changes in expression of cytochrome P450 (P450) genes are a significant issue in the preclinical development of pharmaceuticals. For example, preclinically, P450 induction can affect safety studies by reducing the systemic exposure of a compound undergoing toxicological evaluation, thus limiting the exposure that can be safely investigated in patients. Therefore, the induction potential of candidate drugs has been studied as part of the drug development process, typically using protein and/or catalytic end points.

Effects of behavioral and morphological plasticity on risk of predation in a Neotropical tadpole.

Predator-induced phenotypic plasticity is widespread among aquatic animals, however the relative contributions of behavioral and morphological shifts to reducing risk of predation remain uncertain. We tested the phenotypic plasticity of a Neotropical tadpole ( Rana palmipes) in response to chemical cues from predatory Belostoma water bugs, and how phenotype affects risk of predation. Behavior, morphology, and pigmentation all were plastic, resulting in a predator-induced phenotype with lower activity, deeper tail fin and muscle, and darker pigmentation.