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



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.



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.



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.
Fu
Xu-chun
XC
Department of Pharmacy, Zhejiang University City College, Hangzhou 310015, China.
Sun
Qun
Q
D000319:Adrenergic beta-Antagonists / Q000737:chemistry* / Q000493:pharmacokinetics*; D000818:Animals; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism*; D008790:Metoprolol / Q000493:pharmacokinetics; D015394:Molecular Structure; D009248:Nadolol / Q000493:pharmacokinetics; D011433:Propranolol / Q000493:pharmacokinetics; D051381:Rats; D012044:Regression Analysis
D000319:Adrenergic beta-Antagonists; D009248:Nadolol; D011433:Propranolol; D008790:Metoprolol