GSK2647544 + simvastatin

GSK2647544 + simvastatin is an oral combination of two small molecules: GSK2647544, a selective inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2), and simvastatin, a widely used HMG-CoA reductase inhibitor (statin) for hypercholesterolemia. GSK2647544 was developed primarily for Alzheimer's disease, showing brain penetration and consistent inhibition of Lp-PLA2 in plasma and brain. When administered together, GSK2647544 causes a clinically significant drug-drug interaction by inhibiting CYP3A4, which leads to greatly increased exposure to simvastatin and simvastatin acid. This led to early termination of clinical studies of the combination due to safety concerns[1][2][3][4].