人工神经网络模型在坎地沙坦酯片生物等效性研究中的应用  

Application of artificial neural network model in bioequivalence study of candesartan cilexetil tablets

作　　者：胡殷[1] 杨丹丹[1] 徐毅超 邵蓉[1] 阮邹荣[1] 江波[1] 陈金亮[1] 楼洪刚[1] HU Yin;YANG Dandan;XU Yichao;SHAO Rong;RUAN Zourong;JIANG Bo;CHEN Jinliang;LOU Honggang(Center of Clinical Pharmacology,the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,Zhejiang,China)

机构地区：[1]浙江大学医学院附属第二医院临床药理中心,浙江杭州310009

出　　处：《中国临床药理学与治疗学》2022年第1期63-69,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家卫生健康委重大新药创制国家科技重大专项《心血管疾病防治新药临床评价技术示范性平台建设》(2020ZX09201022)。

摘　　要：目的:评价中国健康受试者单次口服坎地沙坦酯片受试制剂和参比制剂的人体生物等效性,并建立人工神经网络模型,预测人体口服坎地沙坦酯片的血药浓度,为临床合理用药提供依据。方法:筛选32例中国健康受试者在空腹或餐后条件下单次口服8 mg坎地沙坦酯片受试制剂或参比制剂,进行生物等效性研究。利用坎地沙坦生物等效性研究结果,采用MATLAB软件构建反向传播人工神经网络模型,对模型进行内部和外部验证,用于预测人体口服坎地沙坦片后的血药浓度。结果:空腹试验和餐后条件下,受试制剂C_(max)、AUC_(0-t)、AUC_(0-∞)均在参比制剂80.00%-125.00%的等效区间内,两制剂生物等效。利用MATLAB软件构建的坎地沙坦血药浓度预测模型,性能验证结果均方差为0.000 781,梯度幅度为0.000 432,验证检查次数为0,训练组、验证组、预测组的相关系数均大于0.99。结论:受试制剂与参比制剂在空腹和餐后服用的情况下均具有生物等效性,建立的坎地沙坦血药浓度预测模型能准确预测人体口服坎地沙坦酯片的血药浓度,可为临床合理用药提供依据。AIM: To evaluate the bioequivalence of two candesartan cilexetil tablet formulations in healthy Chinese subjects after administration of a single dose, and an artificial neural network model was established to predict the candesartan plasma concentration, and provide a basis for clinical rational use of drugs. METHODS: Thirty-two healthy Chinese subjects were enrolled for oral administration of a single 8 mg dose of candesartan cilexetil tablet(test or reference product) under fasting or fed conditions to conduct a bioequivalence study. The bioequivalence results were used to build a back-propagation artificial neural network model by MATLAB software, and the model was internally and externally verified to predict the plasma concentration. RESULTS: Under both fasting and fed conditions, the C_(max), AUCAUC_(0-t), and AUC_(0-∞)of the test product were all fall within 80.00%-125.00% of the reference product, indicating the two formulations were bioequivalent. The candesartan plasma concentration prediction model was constructed by MATLAB software. The performance verification result of MSE is 0.000 781, the gradient amplitude is 0.000 432, the number of verification checks is 0. Good correlation coefficients are showed in the training group, the verification group, and the prediction group(r>0.99). CONCLUSION: The test and the reference product of candesartan cilexetil are bioequivalent under fasting and fed conditions. The established prediction model can accurately predict the candesartan plasma concentration in humans after oral administration. It may provide a basis for clinical rational use of drugs.

关 键 词：坎地沙坦酯片 生物等效性 人工神经网络 血药浓度 精准医疗 

分 类 号：R969.1[医药卫生—药理学]