[Correlation between absorption rates of beta-adrenoreceptor antagonists in rat small intestine and their molecular structures].

OBJECTIVE

To study the correlation between the absorption rate constants of beta-adrenoreceptor antagonists in rat small intestinal segments and their molecular structural parameters.

METHODS

The 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.

RESULTS

The 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.

CONCLUSION

The absorption rate constants of beta-adrenoreceptor antagonists in rat small intestinal segments are mainly related with their lipophilicity,hydrogen-bonding potential and molecular size.