Pharmacodynamics, pharmacokinetics and safety of GSK2190915, a novel oral anti-inflammatory 5-lipoxygenase-activating protein inhibitor.

摘要: Aim To assess the pharmacokinetics, pharmacodynamics, safety and tolerability of 5-lipoxygenase-activating protein inhibitor, GSK2190915, after oral dosing in two independent phase I studies, one Western European Japanese subjects, utilizing different formulations. Method Western subjects received single (50–1000 mg) or multiple (10–450 mg) doses GSK2190915 placebo a dose-escalating manner. three four (10–200 mg) plus once period crossover design. Blood samples were collected for concentrations blood urine to measure leukotriene B4 E4, respectively, as pharmacodynamic markers drug activity. Results There was no clear difference adverse events between active drug-treated either study. Maximum plasma area under curve increased dose-related manner mean half-life values ranged from 16–34 h. Dose-dependent inhibition production observed near complete urinary E4 excretion shown at all except lowest dose. The EC50 LTB4 85 nm 89 nm respectively. Conclusion GSK2190915 is well-tolerated with pharmacokinetics pharmacodynamics that support daily 24 h leukotrienes. Doses ≥50 mg show post-dose, whereas ≥150 mg are required LTB4.