Dosing Adjustments in Cases of Altered Plasma Protein Binding are Most Needed for Drugs with a Volume of Distribution Below 1.3 L/kg.

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY Clinical Pharmacokinetics Pub Date : 2024-08-01 Epub Date: 2024-07-24 DOI:10.1007/s40262-024-01403-1
Florin M Musteata
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Abstract

Background: The present literature offers conflicting views on the importance of changes in plasma protein binding in clinical therapeutics. Furthermore, there are no methods to calculate a new dosing regimen when such changes occur.

Methods: Previous models developed by Balaz et al. and Greenblat et al. were used to calculate a plasma protein binding (PPB) score for individual drugs based on the volume of distribution for total concentration and the bound fraction of drug. The models were further used to calculate a new drug dosing interval for cases of altered plasma protein binding. The equations apply best for drugs with fast absorption and fast distribution; they can be used as approximations for drugs with slow distribution by using the volume of distribution at steady state and the rate constant of the elimination phase.

Results: The newly developed equations show that changes in plasma protein binding are relevant only for drugs with a positive PPB score; such drugs must have a volume of distribution for total concentration below 1.3 L/kg and high protein binding. It is further shown that the drug dosing interval should be reduced when the remaining fraction of plasma protein binding is below the PPB score.

Conclusion: A new method to rank drugs according to the impact of changes in plasma protein binding on their pharmacokinetic profile was developed. The new method was applied to show that drugs with high PPB scores need reductions in their dosing interval when the level of protein binding decreases.

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对于分布容积低于 1.3 升/千克的药物,最需要在血浆蛋白结合力改变的情况下调整剂量。
背景:关于血浆蛋白结合力变化在临床治疗中的重要性,目前的文献观点不一。此外,当这种变化发生时,还没有计算新给药方案的方法:方法:使用 Balaz 等人和 Greenblat 等人之前开发的模型,根据药物总浓度的分布容积和药物的结合率,计算出单个药物的血浆蛋白结合率(PPB)得分。这些模型还可用于计算血浆蛋白结合力改变情况下的新药剂量间隔。这些方程最适用于吸收快和分布快的药物;对于分布慢的药物,可使用稳态分布容积和消除阶段的速率常数作为近似值:新开发的方程表明,血浆蛋白结合力的变化只与 PPB 评分为正的药物有关;这类药物的总浓度分布容积必须低于 1.3 升/千克,且蛋白结合力较高。研究进一步表明,当剩余的血浆蛋白结合率低于 PPB 评分时,用药间隔应缩短:根据血浆蛋白结合率的变化对药物药代动力学特征的影响,开发了一种对药物进行排序的新方法。应用新方法表明,当蛋白结合水平降低时,PPB 分数高的药物需要缩短用药间隔。
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来源期刊
CiteScore
8.80
自引率
4.40%
发文量
86
审稿时长
6-12 weeks
期刊介绍: Clinical Pharmacokinetics promotes the continuing development of clinical pharmacokinetics and pharmacodynamics for the improvement of drug therapy, and for furthering postgraduate education in clinical pharmacology and therapeutics. Pharmacokinetics, the study of drug disposition in the body, is an integral part of drug development and rational use. Knowledge and application of pharmacokinetic principles leads to accelerated drug development, cost effective drug use and a reduced frequency of adverse effects and drug interactions.
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