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

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dc.contributor.authorMusteata, Florin Marcel
dc.date.accessioned2025-02-04T17:31:34Z
dc.date.available2025-02-04T17:31:34Z
dc.date.issued2024-08
dc.descriptionClick on the Resource Link to access the article (may not be free).
dc.description.abstractBackground: 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
dc.description.grantGrant Funded
dc.description.sponsorship1R15GM126510/Foundation for the National Institutes of Health
dc.description.urihttps://doi.org/10.1007/s40262-024-01403-1
dc.identifier.citationMusteata FM. Dosing Adjustments in Cases of Altered Plasma Protein Binding are Most Needed for Drugs with a Volume of Distribution Below 1.3 L/kg. Clin Pharmacokinet. 2024 Aug;63(8):1111-1119. doi: 10.1007/s40262-024-01403-1. Epub 2024 Jul 24. PMID: 39044110.
dc.identifier.issn0312-5963
dc.identifier.other39044110
dc.identifier.urihttps://hdl.handle.net/20.500.14303/684
dc.language.isoen
dc.publisherADIS Press
dc.relation.ispartofClinical Pharmacokinetics
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dc.subjectProtein Binding
dc.subjectBlood Proteins
dc.titleDosing Adjustments in Cases of Altered Plasma Protein Binding are Most Needed for Drugs with a Volume of Distribution Below 1.3 L/kg.
dc.typeArticle
local.departmentprogramDepartment of Pharmaceutical Sciences
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