Distribution Clearance: Significance and Underlying Mechanisms.

IF 3.5 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Pharmaceutical Research Pub Date : 2024-07-01 Epub Date: 2024-07-09 DOI:10.1007/s11095-024-03738-7

Michael Weiss

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引用次数: 0

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_D) in this respect.

Methods: Since mammillary compartmental models are widely used, CL_D 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_D allowed a comparison of distributional properties of different drugs and provided physiological insight. Significant changes in CL_D were observed as a result of drug-drug interactions, transporter polymorphisms and a diseased state.

Conclusion: Total distribution clearance CL_D 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.

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分布清理：意义和基本机制。

目的：分布动力学评估是药代动力学中被忽视的一个方面。本研究探讨了与模型无关的参数全身分布清除率（CLD）在这方面的作用：方法：由于乳腺区室模型被广泛使用，因此根据该模型的参数计算了 15 种药物的 CLD。通过评估与药代动力学参数和协变量的关系，探讨了基本分布过程：结果：参数 CLD 的定义与模型无关，因此可以比较不同药物的分布特性，并提供生理学见解。由于药物之间的相互作用、转运体多态性和疾病状态，CLD发生了显著变化：总分布清除率 CLD 是评估药物分布动力学的一个有用参数。结论：总分布清除率 CLD 是评估药物分布动力学的有用参数，建议将其作为与模型无关的清除率和稳态分布容积参数的辅助参数进行估算。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.