Retention pharmacokinetic and pharmacodynamic parameter relationships of antihistamine drugs using biopartitioning micellar chromatography

Antihistamines are drugs which act by competitive inhibition of the H-1 or H-2 histamine receptors. Little has been known about their clinical pharmac okinetics and biological responses until the last few years. In this paper, we propose quantitative retention-activity relationship, QRAR, models base d on the retention data of antihistamines in a biopartitioning micellar chr omatography (BMC) system using a Brij35 mobile phase for describing pharmac okinetic parameters such as half-life and volume of distribution, or the ph armacodynamic parameters, therapeutic plasma levels, lethal doses and drug- receptor dissociation constant. The predictive ability of these models is s tatistically validated. These results are compared to traditional quantitat ive 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, electr onic and steric characteristics which are of great importance in pharmacoki netic and pharmacodynamic behavior. (C) 2001 Elsevier Science B.V. All righ ts reserved.