preclinical screening oral bioavailability predictio human oral bioavailability human vd and cl prediction animal correlation predicting human t1/2 enzyme kinetic method invitro t1/2 method predicting human clearance allometry corrected for pb allometry without protein bind proportionality method average fraction unbound human volume of distribution predicting human vd predicting pharmacokinetics pbpk modelling allometric scaling isometric scaling preclinical to clinical data extrapolation glucose uptake assay alpha amylase inhibition assay spontaneously diabetic rats genetically diabetic models virus induced diabetes dm preclinical screening streptozotocin induced dm triphasic response alloxan induced diabetes antidiabetics inside out configuration outside out configuration whole cell mode cell attached mode patch clamp technique carbonic anhydrase inhibition clearance methods diuretic activity saluretic activity lipschitz test diuretics
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