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Benoxaprofen: plasma binding and binding interactions with some drugs and endogenous compounds
European Journal of Rheumatology and Inflammation
|January 1, 1982
Summary
Benoxaprofen extensively binds to human serum albumin (HSA), with binding exceeding 99.5% at normal concentrations. Liver failure with high bilirubin levels slightly reduces binding, while certain other drugs can displace benoxaprofen from HSA.
Area of Science:
- Pharmacology
- Biochemistry
- Clinical Chemistry
Background:
- Benoxaprofen is an acidic drug extensively bound by plasma proteins.
- Human serum albumin (HSA) is the primary binding protein for many drugs in circulation.
- Understanding drug-protein binding is crucial for predicting pharmacokinetics and pharmacodynamics.
Purpose of the Study:
- To investigate the binding parameters of benoxaprofen to human serum albumin (HSA).
- To assess the impact of physiological conditions (pH, temperature) and disease states (liver failure) on benoxaprofen-HSA binding.
- To evaluate the influence of co-administered drugs on benoxaprofen's serum protein binding.
Main Methods:
- Equilibrium dialysis was employed to determine binding constants and affinities.
- Binding was studied at physiological pH (7.4) and temperature (37°C).
- Interactions with endogenous substances (bilirubin, free fatty acids) and other drugs were examined.
Main Results:
- Benoxaprofen exhibits high affinity binding to HSA, with two binding sites (n1=3.3, K1=3.25x10^5 M⁻¹; n2=16.2, K2=2.1x10³ M⁻¹).
- At normal human plasma concentrations, benoxaprofen binding to HSA exceeded 99.5%.
- Severe hyperbilirubinemia (bilirubinaemia > 130 µM) significantly decreased benoxaprofen binding (p<0.05), while mild hyperbilirubinemia showed no significant effect.
Conclusions:
- Benoxaprofen is highly protein-bound to HSA, suggesting limited free drug concentration under normal physiological conditions.
- Liver failure with severe hyperbilirubinemia can impair benoxaprofen binding, potentially increasing free drug levels.
- Co-administration with certain drugs, like furosemide, CPIB, and salicylic acid, can slightly reduce benoxaprofen binding, while benoxaprofen can displace other drugs like CPIB and phenylbutazone.