Predicting Protein Binding of Drugs Using Abraham Parameters: Effect of Ionization

Abstract

Background and purpose: Protein binding (PB) is an important pharmacokinetic parameter in drug discovery and development. In past years Abraham parameters were used to predict some physicochemical and pharmacokinetic properties of drugs. But in these cases, the ionization of drugs in blood pH (7.4) was ignored. Recently, Abraham parameters of chemical compounds in ionized form are proposed. Also, Henderson Hasselbalch equation could be used to calculate the percent ionization of drugs. In this study, Abraham parameters were calculated according to the ionized fraction of drug and PB was predicted using these parameters. Materials and methods: PB data points of 159 drugs were collected from the literature. Abraham parameters of drugs were calculated according to the percentage of ionization in blood pH=7.4. The models were built up based on the multiple linear regression (MLR) analysis and percentage error of each model was computed. Results: Findings showed a linear relation between PB and Abraham parameters based on the ionized fraction in blood pH, so, the developed model could predict the PB better than the model established by Abraham parameters in :union:ized form. Conclusion: Ionization of drugs in blood pH is an essential parameter in predicting PB, and Abraham parameters for ionized form of drug can be used to predict it with a good accuracy.

Keywords

• drug
• protein binding
• prediction
• modeling
• ionization