目的 基于生理驅(qū)動建立生理藥動學(xué)（PBPK）模型，以酒石酸美托洛爾緩釋片、氨茶堿緩釋片、吲達帕胺緩釋片和奧美拉唑腸溶片為工具藥進行模型預(yù)測準確性考察。方法 將氨茶堿緩釋片、酒石酸美托洛爾緩釋片、奧美拉唑腸溶片、吲達帕胺緩釋片的相關(guān)參數(shù)帶入生理驅(qū)動V1.0平臺，預(yù)測血藥濃度，計算藥動學(xué)參數(shù)。雄性Beagle犬ig受試藥物1片（吲噠帕胺緩釋片1.5 mg、奧美拉唑腸溶片60 mg、酒石酸美托洛爾緩釋片50 mg、氨茶堿緩釋片100 mg），于給藥前和給藥后0.5、1.0、1.5、2.0、3.0、4.0、5.0、7.0、9.0、12.0、16.0、24.0、36.0、48.0 h犬前肢靜脈取血；建立超高效液相色譜-三重四級桿串聯(lián)質(zhì)譜（UPLC-MS/MS）法檢測Beagle犬血藥濃度，并計算藥動學(xué)參數(shù)。對血藥濃度預(yù)測結(jié)果和實測結(jié)果進行相關(guān)性分析；對藥動學(xué)參數(shù)進行誤差分析。結(jié)果 成功建立基于生驅(qū)動的人體及比格犬外推PBPK模型，氨茶堿緩釋片、酒石酸美托洛爾緩釋片、奧美拉唑腸溶片血藥濃度實測值與預(yù)測值較接近，吲達帕胺緩釋片的實測峰濃度低于預(yù)測值，相關(guān)系數(shù)分別為0.933 1、0.974 3、0.918 8、0.965 8。藥動學(xué)參數(shù)誤差分析C_max誤差分別為22%、27%、10%、32%，AUC誤差分別為-13%、-9%、-14%、-6%，T_max的誤差分別為-40%、-15%、25%、-110%，t_1/2的誤差分別為-17%、-11%、-46%、52%。T_max和t_1/2的預(yù)測與實測值差距較大，對奧美拉唑腸溶片的預(yù)測誤差均小于25%，預(yù)測準確。吲達帕胺緩釋片的C_max和t_1/2預(yù)測誤差均較大，可能是犬的消化道內(nèi)的消化液的總量比人少，使難溶性藥物吲達帕胺的溶解更加困難造成的。結(jié)論 基于生理驅(qū)動的PBPK模型能比較準確的預(yù)測生物藥劑學(xué)分類系統(tǒng)（BCS）Ⅰ類的酒石酸美托洛爾緩釋片、氨茶堿緩釋片、Ⅱ類吲達帕胺緩釋片和奧美拉唑腸溶片的吸收程度與藥動學(xué)特征。

Objective Based on the physiological engine PBPK model, the prediction accuracy was evaluated with metoprolol sustained-release tablets, aminophylline sustained-release tablets, indapamide sustained-release tablets and omeprazole entericcoated tablets as tool drugs. Methods The related parameters of aminophylline sustained-release tablets, metoprolol tartrate sustained-release tablets, omeprazole enteric coated tablets and indapamide sustained-release tablets were brought into the physiological driving v1.0 platform to predict the blood concentration and calculate the pharmacokinetic parameters. One tablet (indapamide 1.5 mg, omeprazole 60 mg, metoprolol tartrate 50 mg, aminophylline 100 mg) was given to male beagle dogs. Venous blood collected from dog forelimb before administration and 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 7.0, 9.0, 12.0, 16.0, 24.0, 36.0, 48.0 h after administration. A method of ultra-high performance liquid chromatography triple quadrupole tandem mass spectrometry (UPLC-MS/MS) was established for the determination of beagle dogs' blood drug concentration, and the pharmacokinetic parameters were calculated. The correlation between the predicted results and the measured results was analyzed, and the error of pharmacokinetic parameters was analyzed. Results Successfully established a human-driven human body and beagle dog extrapolation PBPK model, The predicted results of the aminophylline sustained-release tablets, omeprazole enteric-coated tablets, metoprolol sustained-release tablets and indapamide sustained-release tablets in the Beagle dog extrapolation model compared with Beagle's in vivo data, The correlation is 0.9331, 0.9743, 0.9188, 0.9658, The C_max error of the pharmacokinetic parameter error analysis were 22%, 27%, 10%, 32%, AUC errors were-13%,-9%,-14%,-6%, The error of T_max were-40%,-15%, 25%,-110%, The error of T_1/2 were-17%,-11%,-46%, 52%. The difference between T_max and t_1/2 were large, and the prediction error of omeprazole enteric coated tablets was less than 25%. The C_max and t_1/2 prediction errors of indapamide sustained-release tablets are large, which may be caused by the fact that the total amount of digestive fluid in the digestive tract of dogs is less than that of people, making the dissolution of indapamide more difficult. Conclusion The PBPK model based on physiological engine could accurate predict pharmacokinetic characteristics.of the absorption with metoprolol sustained-release tablets, aminophylline sustained-release tablets (BCSI), class indapamide sustained-release tablets and omeprazole enteric-coated tablets(BCSII).

廣東省基礎(chǔ)與應(yīng)用基礎(chǔ)研究基金項目（2020A1515010156）；廣東省普通高校人工智能重點領(lǐng)域?qū)ｍ棧?019KZDZX1006）；2019年度廣東省重點學(xué)科科研項目