Background and Rationale: Physiologically-based pharmacokinetics (PBPK) modelling is a key component of model-based drug development and is increasingly embraced within the industry and regulatory authorities.PBPK is a useful tool to simulate PK profiles in various ethnic groups and can be used as the first step to assess ethnic sensitivity.Currently, commercially available PBPK models use parameters gathered mainly in Caucasians while the population data in Chinese is yet to be collected.In addition, the data and model of Chinese population are new and need more evaluation for prospective application.Objective:Firstly, to.evaluate the omeprazole PBPK model in Chinese, assess the likely ethnical differences between Chinese and Caucasian populations in the kinetics of CYP2C19 substrates arising from demographic, physiological and genetic differences and design better bridge clinical studies.Secondly, to predict the difference in pharmacokinetics of Omeprazole in Caucasian and Chinese using the qualified model.Method:Omeprazole PBPK model built by SimCYP (Version 12) was applied through incorporating Chinese population specific data (demographic, physiological and enzyme information) collated from literature sources [1].The omeprazole model consists of Advanced Dissolution, Absorption and Metabolism (ADAM) Model and minimal PBPK model for absorption and volume of distribution, respectively.The clearance is scaled using the following equation for both CYP3A4 and CYP2C19 pathways: CLuH,int=CLu,int×abundance×MPPGL×Liver weight[2].MPPGL is microsomal protein per gram of liver.The published in vivo PK data in Chinese were used as the observed values.Omeprazole was administrated orally in two papers and intravenously in one paper [3-5].Virtual subjects (n=100) generated within SimCYP are matched to the subjects used in the published papers with respect to age, body weight, height, sex, dosage and phenotype.CYP2C19 is known as the major metabolic pathway of Omeprazole for the extensive metabolizers (EM), and the genotypes of*1/*1, *1/*2, *1/*3 are known as the EMs.The PK data of the EM subjects are used to evaluate the model in Chinese for the CYP2C19 substrate Omeprazole.Similarly, the PK data of the PM subjects are used for the PM model evaluation (i.e., CYP3A4 metabolism of Omeprazole).This is accomplished by plotting the observed data of individual subjects overlaying with the model based 90% prediction interval (shaded area).In addition, the PK parameters (AUC and Cmax) are compared.Once the model is confirmed with acceptable errors, simulations of the population PKs of Omeprazole in both Chinese and Caucasians can be produced based on the frequencies of EM and PM for 2C19 in the two populations and their differences can be calculated.Result:Discussion and conclusion:The discrepancy between simulation and observation is within 2-fold.The existing CYP2C19 data in the Simcyp can be used to simulate PK of CYP2C 19 substrates in Chinese.The difference in PK of omeprazole in Caucasian and Chinese may be mainly caused by the difference of abundance of CYP2C 19 followed by body weight.Extension of this work to predict PK of other CYP substrates in Chinese is indicated.