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分布清除：意义和潜在机制。

Distribution Clearance: Significance and Underlying Mechanisms.

机构信息

Department of Pharmacology, Martin Luther University Halle-Wittenberg, Magdeburger Straße 20 (Saale), 06112, Halle, Germany.

出版信息

Pharm Res. 2024 Jul;41(7):1391-1400. doi: 10.1007/s11095-024-03738-7. Epub 2024 Jul 9.

DOI:10.1007/s11095-024-03738-7
PMID:38981900
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11263435/
Abstract

PURPOSE

Evaluation of distribution kinetics is a neglected aspect of pharmacokinetics. This study examines the utility of the model-independent parameter whole body distribution clearance (CL) in this respect.

METHODS

Since mammillary compartmental models are widely used, CL was calculated in terms of parameters of this model for 15 drugs. The underlying distribution processes were explored by assessment of relationships to pharmacokinetic parameters and covariates.

RESULTS

The model-independence of the definition of the parameter CL allowed a comparison of distributional properties of different drugs and provided physiological insight. Significant changes in CL were observed as a result of drug-drug interactions, transporter polymorphisms and a diseased state.

CONCLUSION

Total distribution clearance CL is a useful parameter to evaluate distribution kinetics of drugs. Its estimation as an adjunct to the model-independent parameters clearance and steady-state volume of distribution is advocated.

摘要

目的

分布动力学的评估是药物动力学中被忽视的一个方面。本研究探讨了模型独立参数全身分布清除率（CL）在这方面的应用。

方法

由于乳突室 compartmental 模型被广泛应用，CL 是根据该模型的参数计算的，用于 15 种药物。通过评估与药代动力学参数和协变量的关系，探讨了潜在的分布过程。

结果

参数 CL 的定义的模型独立性允许比较不同药物的分布特性，并提供了生理学上的见解。药物相互作用、转运体多态性和疾病状态导致 CL 发生显著变化。

结论

总分布清除率 CL 是评估药物分布动力学的有用参数。建议将其作为模型独立参数清除率和稳态分布容积的辅助参数进行估算。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34c1/11263435/21b423f4a27c/11095_2024_3738_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34c1/11263435/71bcdc0de8e7/11095_2024_3738_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34c1/11263435/d37756d5c157/11095_2024_3738_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34c1/11263435/21b423f4a27c/11095_2024_3738_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34c1/11263435/71bcdc0de8e7/11095_2024_3738_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34c1/11263435/d37756d5c157/11095_2024_3738_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34c1/11263435/21b423f4a27c/11095_2024_3738_Fig3_HTML.jpg

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Consideration of Fractional Distribution Parameter f in the Chen and Gross Method for Tissue-to-Plasma Partition Coefficients: Comparison of Several Methods.考虑 Chen 和 Gross 方法中组织-血浆分配系数的分数分布参数 f：几种方法的比较。
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依托于延长释放型氯胺酮给药，对其对映异构体及其代谢物的药代动力学模型进行研究，并着重研究 2,6-羟去甲氯胺酮。
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