Retention pharmacokinetic and pharmacodynamic parameter relationships of antihistamine drugs using biopartitioning...

Antihistamines are drugs which act by competitive inhibition of the H1 or H2 histamine receptors. Little has been known about their clinical pharmacokinetics and biological responses until the last few years. In this paper, we propose quantitative retention-activity relationship, QRAR, models based on the retention data of antihistamines in a biopartitioning micellar chromatography (BMC) system using a Brij35 mobile phase for describing pharmacokinetic parameters such as half-life and volume of distribution, or the pharmacodynamic parameters, therapeutic plasma levels, lethal doses and drug-receptor dissociation constant. The predictive ability of these models is statistically validated. These results are compared to traditional quantitative structure-activity relationship, QSAR, models using lipophilicity data. The adequacy of QRAR models can be explained taking into account the fact that the retention of compounds in BMC depends on their hydrophobic, electronic and steric characteristics which are of great importance in pharmacokinetic and pharmacodynamic behavior.