1.Correlation between absorption rates of beta-adrenoreceptor antagonists in rat small intestine and their molecular structures.
Journal of Zhejiang University. Medical sciences 2005;34(2):177-180
OBJECTIVETo study the correlation between the absorption rate constants of beta-adrenoreceptor antagonists in rat small intestinal segments and their molecular structural parameters.
METHODSThe net atomic charges and the molecular volumes of 11 beta-adrenoreceptor antagonists were obtained with the semiempirical self-consistent field molecular orbital calculation CNDO/2 method and Mont Carlo method respectively, using the minimum energy conformation obtained from the optimization of the standard molecular geometry with the molecular mechanics MM+ method. The stepwise multiple regression analysis was used to obtain the correlation equations.
RESULTSThe absorption rate constants of beta-adrenoreceptor antagonists in rat jejunum or ileum were well linearly correlated with the sum of the net charges of all hydrogen atoms and the molecular volumes. The beta-adrenoreceptor antagonist with higher lipophilicity, weaker hydrogen-bonding potential,and smaller molecular volume had greater absorption rate constants.
CONCLUSIONThe absorption rate constants of beta-adrenoreceptor antagonists in rat small intestinal segments are mainly related with their lipophilicity,hydrogen-bonding potential and molecular size.
Adrenergic beta-Antagonists ; chemistry ; pharmacokinetics ; Animals ; Intestinal Absorption ; Intestine, Small ; metabolism ; Metoprolol ; pharmacokinetics ; Molecular Structure ; Nadolol ; pharmacokinetics ; Propranolol ; pharmacokinetics ; Rats ; Regression Analysis