The correlation of plasma protein binding and molecular properties of selected antifungal drugs - Short Communication

Jadranka V. Odović, Milkica A Crevar Sakač, Zorica B Vujić

Abstract


Antifungal agents are group of drugs commonly prescribed in tre­atment of fungal infections which are widely spread among global popu­lation. Their properties such as absorption, distribution, metabolism, route of elimi­na­tion or plasma protein binding (PPB), considerably influence their therapeutic success, while number of drug’s molecular physicochemical pro­perties notably influence all these processes. Lipophilicity (log P), mole­cular weight (Mw), volume (Vol), polar surface area (PSA) and solubility (log S) play important roles in drug absorption, penetration into tissues, distribution and route of eli­mination or the degree of plasma protein binding. In this study, the relation­ships between these five molecular properties of eight antifungal drugs and their plasma protein binding data obtained from relevant literature were inves­ti­gated. The drug’s selected physicochemical molecular descriptors were calcu­lated using software packages. The relationships between PPB and PSA; Mw; Vol and log S were established showing relatively poor correlation (r<0.35). The best correlation was obtained for the relationship between PPB data and lipophilicity descriptor X log P3 (correlation coefficient r = 0.55). In further in­vestigation, multiple linear regression analysis was applied. The best correla­tion was obtained with application of lipophilicity with polar surface area (r = 0.918) and volume (r = 0.916) or molecular weight (= 0.896) as inde­pendent variables.


Keywords


Antimycotics; therapeutic success; lipophilicity; polar surface area; molecular weight; volume; solubility

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DOI: https://doi.org/10.2298/JSC190925125O

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