Peña Juana, Carbo Marcel Li, Solans Anna, Nadal Teresa, Izquierdo Iñaki, Merlos Manuel
Pharmacokinetic & Bioanalysis Department, Palau Pharma SA, Barcelona, Spain.
Eur J Drug Metab Pharmacokinet. 2008 Apr-Jun;33(2):107-16. doi: 10.1007/BF03191027.
Rupatadine is a new oral antihistaminic agent used for the management of allergic inflammatory conditions, such as rhinitis and chronic urticaria. The aim of the present study was to develop a population pharmacokinetic/pharmacodynamic (PKPD) model for the description of the effect of rupatadine and one of its active metabolites, desloratadine, on the histamine-induced flare reaction and to predict the response to treatment after repeated administrations of rupatadine. Both rupatadine and desloratadine were characterized by two-compartmental kinetics. For both compounds, covariates sex and weight had a significant effect on several parameters. The pharmacodynamics were described by an indirect model for the inhibition of flare formation that accounted for the contribution of both rupatadine and desloratadine to the antihistaminic effect. The final PKPD model adequately described the original data. The simulated response after repeated once-daily administrations of 10 mg rupatadine showed a significant and maintained antihistaminic effect over time, between two consecutive dosing intervals.
卢帕他定是一种新型口服抗组胺药，用于治疗过敏性炎症性疾病，如鼻炎和慢性荨麻疹。本研究的目的是建立一个群体药代动力学/药效学（PKPD）模型，以描述卢帕他定及其活性代谢物之一地氯雷他定对组胺诱导的风团反应的影响，并预测卢帕他定重复给药后的治疗反应。卢帕他定和地氯雷他定均具有二室动力学特征。对于这两种化合物，协变量性别和体重对几个参数有显著影响。药效学通过抑制风团形成的间接模型进行描述，该模型考虑了卢帕他定和地氯雷他定对抗组胺作用的贡献。最终的PKPD模型充分描述了原始数据。每天一次重复给予10 mg卢帕他定后的模拟反应显示，在两个连续给药间隔之间，随着时间的推移，抗组胺作用显著且持续。
