TPN729MA is a novel selective phosphodiesterase type 5 (PDE5) inhibitor.The preclinical PK of TPN729MA was studied in rats and dogs.Human clearance (CL) values of TPN729MA were predicted from various allometric methods and from intrinsic CL determined in human liver microsomes (HLM).Human PK and plasma concentration versus time profiles of TPN729MA were predicted by using a physiologically based pharmacokinetic (PBPK) model in GastroPlus.TPN729MA displayed moderate-to-high CL in rats and dogs;the plasma CL was 69.7 ml/(min·kg) in rats and 26.3 ml/(min·kg) in dogs.The steady-state volumes of distribution (Vss) of 7.35 L/kg in rats and 6.48 L/kg in dogs were greater than the total body water.Oral bioavailability of TPN729MA was 10% in rats and > 34% in dogs.Prediction of CL using intrinsic CL in HLM, single-species allometric scaling, and a two-species scaling method provided close estimates of CL.The mean value of these estimates was 10.8 ml/(min·kg) (high CL).