The impact of oxidative stress on binding of drugs with plasma proteins studied by fluorescence anisotropy methods.

The aim of this study was to investigate the effect of oxidative stress on drug binding affinity, free and bound fraction. The fluorescence anisotropy method was used to examine the interactions of commercial human serum albumin (HSA) and human plasma proteins with ochratoxin A (OTA) or carboxylate form of camptothecin (CPT-C). In-vitro method revealed significant reduction in bound fraction of drugs to HSA oxidized by chloramine T. Oxidative stress was determined by measuring the plasma level of advanced oxidation protein products (AOPP). A significant positive correlation between the AOPP and the plasma free fraction of tested drugs in thirty healthy patients was also found. The oxidative stress monitoring by AOPP is very important for improvement of dosage of drugs highly bound to albumin and with narrow therapeutic index. As a result of severe oxidative stress, the drug pharmacokinetics and therapeutic effects are prone to change. This study highlights the issues of therapeutic drug monitoring and it can explain the behaviour of drugs in pathological situations.