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Reprint of “Pharmacokinetic modelling of the anti-malarial drug artesunate and its active metabolite dihydroartemisinin”

机译：重印“抗疟药青蒿琥酯及其活性代谢物二氢青蒿素的药代动力学模型”

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摘要

A four compartment mechanistic mathematical model is developed for the pharmacokinetics of the commonly used anti-malarial drug artesunate and its principle metabolite dihydroartemisinin following oral administration of artesunate. The model is structurally unidentifiable unless additional constraints are imposed. Combinations of mechanistically derived constraints are considered to assess their effects on structural identifiability and on model fits. Certain combinations of the constraints give rise to locally or globally identifiable model structures.\ud\udInitial validation of the model under various combinations of the constraints leading to identifiable model structures was performed against a dataset of artesunate and dihydroartemisinin concentration–time profiles of 19 malaria patients. When all the discussed constraints were imposed on the model, the resulting globally identifiable model structure was found to fit reasonably well to those patients with normal drug absorption profiles. However, there is wide variability in the fitted parameters and further investigation is warranted.
机译：针对青蒿琥酯口服后常用的抗疟药青蒿琥酯及其主要代谢产物双氢青蒿素的药代动力学，建立了一个四室力学数学模型。除非施加其他约束，否则该模型在结构上无法识别。考虑将机械派生的约束组合起来，以评估它们对结构可识别性和模型拟合的影响。约束的某些组合会产生局部或全局可识别的模型结构。\ ud \ ud在各种约束条件组合下（可识别模型结构的情况下）对模型的初始验证是针对青蒿琥酯和双氢青蒿素浓度-19种疟疾的时间分布图数据集进行的耐心。当将所有讨论的约束条件强加给模型时，发现所得的全局可识别模型结构非常适合那些具有正常药物吸收曲线的患者。但是，拟合参数存在很大差异，因此有必要进行进一步研究。

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