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Pharmacokinetic interaction between endogenous cortisol and exogenous corticosteroids
S Rohatagi1, G Hochhaus, H Möllmann
1Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainsville, USA.
Die Pharmazie
|September 1, 1995
Summary
Evaluating drug interactions between prednisolone and cortisol is complex due to shared protein binding. This study presents a computational method to accurately calculate free corticosteroid concentrations, accounting for pharmacokinetic and pharmacodynamic interactions.
Area of Science:
- Pharmacology
- Biochemistry
- Computational Biology
Background:
- Prednisolone and cortisol share binding sites on cortisol binding globulin (CBG) and albumin.
- CBG binding for both steroids is saturable within therapeutic ranges, complicating interaction evaluation.
- Accurate assessment of active free corticosteroid concentrations is crucial for understanding drug interactions.
Purpose of the Study:
- To develop a computational method for accurately calculating free prednisolone and cortisol concentrations.
- To account for pharmacokinetic and pharmacodynamic interactions between these two steroids.
- To improve the estimation of active free corticosteroid levels in clinical settings.
Main Methods:
- Applied general drug binding equations to a two-drug, two-site model, deriving implicit cubic equations.
- Utilized a personal computer spreadsheet program (EXCEL 5.0 with SOLVER) to solve these complex equations.
- Simulated free concentrations of prednisolone and cortisol as a function of their total concentrations.
Main Results:
- Protein binding of cortisol is stable in physiological ranges but affected by exogenous corticosteroids.
- Exogenous corticosteroid binding to CBG is influenced by competing endogenous cortisol concentrations.
- Exogenous corticosteroids were shown to suppress endogenous cortisol release.
Conclusions:
- The developed computational approach accurately estimates active free corticosteroid concentrations.
- This method effectively integrates pharmacokinetic and pharmacodynamic interactions for improved drug interaction evaluation.
- The findings enhance the understanding of steroid-steroid interactions and their clinical implications.