口服溴溴化物的群体药代动力学：着重于吸收过程。,European Journal of Pharmaceutical Sciences

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口服溴溴化物的群体药代动力学：着重于吸收过程。
European Journal of Pharmaceutical Sciences ( IF 4.3 ) Pub Date : 2019-10-25 , DOI: 10.1016/j.ejps.2019.105081
Larissa Lachi-Silva ₁ , Aline B Barth ₁ , Gustavo Mendes Lima Santos ₂ , Malidi Ahamadi ₁ , Marcos Luciano Bruschi ₃ , Elza Kimura ₄ , Bibiana Verlindo de Araújo ₅ , Andréa Diniz ₁

Affiliation

Bromopride是用于治疗恶心和呕吐的促动力和止吐药。尽管它的处方在巴西很常见，但是缺乏关于溴溴化物药代动力学的研究。因此，本研究的目的是研究溴溴化物的总体药代动力学，并评估协变量对其吸收的影响。这项研究是对从生物等效性研究收集的数据的回顾性分析。数据使用MONOLIX 2018R2建模。假定一室和线性消除，吸收相用不同的结构模型进行了评估。具有所有参数的组合误差和指数个体间变异性的顺序一阶和零阶模型可以最好地描述溴化物的非典型吸收曲线。总体估计是一阶吸收率（ka）为0。08 h-1，一级吸收的剂量分数（Fr）为32.60％，零级吸收的持续时间（Tk0）为0.88 h，潜伏时间（Tlag）为0.47 h，分配体积为230 l，清除率46.80 lh-1.体重影响Tk0，剂型与Tk0和Tlag相关，而性别影响Tlag。但是，评估这些协变量在稳态下的临床重要性的模拟表明，溴溴化物暴露的变化很小。混合吸收模型可以合理地描述溴溴化物的吸收过程，因为它具有适应多峰分布的灵活性，并且与药物的理化性质具有很好的一致性。分布体积为230 l，清除率为46.80 lh-1.体重影响Tk0，发现剂型与Tk0和Tlag相关，而性别则影响Tlag。但是，评估这些协变量在稳态下的临床重要性的模拟表明，溴溴化物暴露的变化很小。混合吸收模型可以合理地描述溴溴化物的吸收过程，因为它具有适应多峰分布的灵活性，并且与药物的理化性质具有很好的一致性。分布体积为230 l，清除率为46.80 lh-1。体重影响Tk0，剂型与Tk0和Tlag相关，而性别影响Tlag。但是，评估这些协变量在稳态下的临床重要性的模拟表明，溴溴化物暴露的变化很小。混合吸收模型可以合理地描述溴溴化物的吸收过程，因为它具有适应多峰分布的灵活性，并且与药物的理化性质具有很好的一致性。

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Population pharmacokinetics of orally administrated bromopride: Focus on the absorption process.

Bromopride is a prokinetic and antiemetic drug used to treat nausea and vomiting. Although its prescription is common in Brazil, there is a lack of studies about bromopride pharmacokinetics. Therefore, the aims of this study were to investigate the population pharmacokinetics of bromopride and to evaluate the influence of covariates on its absorption. This study is a retrospective analysis of data collected from bioequivalence studies. The data was modeled using MONOLIX 2018R2. Assuming one-compartment and linear elimination, the absorption phase was evaluated with different structural models. The model of sequential first- and zero-order with combined error and exponential inter-individual variability in all parameters best described the atypical absorption profile of bromopride. Population estimates were first-order absorption rate (ka) of 0.08 h - 1, fraction of dose absorbed by first-order (Fr) of 32.60%, duration of the zero-order absorption (Tk0) of 0.88 h with latency time (Tlag) of 0.47 h, volume of distribution of 230 l and clearance of 46.80 l h - 1. Bodyweight affects Tk0, dosage form was found to correlate with Tk0 and Tlag, while gender affects Tlag. However, simulations evaluating the clinical importance of these covariates on steady-state indicated minimal changes on bromopride exposure. The mixed absorption model was reasonable to describe the absorption process of bromopride because it had the flexibility to fit multiple-peaks profile and shows good agreement with physicochemical properties of drug.

更新日期：2019-10-25

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