Time dependent inhibition of CYP3A4 (unknown origin) at 100 uM preincubated up to 15 mins followed by 7-benzyloxy-trifluoromethylcoumarin substrate and NADPH addition by fluorescence assay
Antagonist activity at rat TRPV4 expressed in BHK/AC9 cells assessed as inhibition of GSK634775-induced calcium immobilization pre-incubated for 10 mins followed by agonist addition by Fluo-4-AM dye-based FLIPR assay
Fraction unbound in Sprague-Dawley rat heart failure-induced pulmonary edema model at 0.09 to 0.78 mg/kg, iv bolus loading dose followed by 0.07 to 0.6 ug/kg/min, iv continuous infusion dose for 60 mins
Reversal of heart failure-induced pulmonary edema in Sprague-Dawley rat assessed as inhibition of GSK1016790A-induced increase in lung wet weight to body weight ratio at 0.09 to 0.78 mg/kg, iv bolus loading dose followed by 0.07 to 0.6 ug/kg/min, iv continuous infusion dose for 60 mins prior to agonist administration
Antagonist activity at human TRPV4 expressed in BHK/AC9 cells assessed as inhibition of GSK634775-induced calcium immobilization pre-incubated for 10 mins followed by agonist addition by Fluo-4-AM dye-based FLIPR assay
Plasma concentration in Sprague-Dawley rat heart failure-induced pulmonary edema model at 0.09 mg/kg, iv bolus loading dose followed by 0.07 ug/kg/min, iv continuous infusion dose for 60 mins
Plasma concentration in Sprague-Dawley rat heart failure-induced pulmonary edema model at 0.26 mg/kg, iv bolus loading dose followed by 0.2 ug/kg/min, iv continuous infusion dose for 60 mins
Plasma concentration in Sprague-Dawley rat heart failure-induced pulmonary edema model at 0.78 mg/kg, iv bolus loading dose followed by 0.6 ug/kg/min, iv continuous infusion dose for 60 mins
Reversal of heart failure-induced pulmonary edema in Sprague-Dawley rat assessed as inhibition of GSK1016790A-induced increase in lung wet weight to body weight ratio at 0.26 mg/kg, iv bolus loading dose followed by 0.2 ug/kg/min, iv continuous infusion dose for 60 mins prior to agonist administration relative to control