title: [Prediction of human intestinal absorption from net polar atomic charges of drug molecules].
abstract: To predict human intestinal absorption and permeability coefficients in Caco-2 cell monolayers from net polar atomic charges of drug molecules.
  
  
  
  The net atomic charges and the volumes of drug molecules 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.
  
  
  
  Both percent of human intestinal absorption and permeability coefficients in Caco-2 cell monolayers of drug molecules were well correlated with the sum of the net atomic charges of all hydrogen-bonding donors (sigmaQH) and the sum of the net atomic charges of all hydrogen-bonding acceptors (sigmaQN, 0). The more the net positive atomic charges of hydrogen-bonding donors and the net negative atomic charges of hydrogen-bonding acceptors, the less were the percent human intestinal absorption and permeability coefficients in Caco-2 cell monolayers of drug molecules.
  
  
  
  Drug absorption in human intestines is closely related with its hydrogen-bonding potential. The drug molecules with weaker hydrogen-bonding potential have greater percent human intestinal absorption. The net polar atomic charges can be computed simply, so they can be used in high throughput screening of oral drugs.
authors.affiliation: Department of Pharmacy, Zhejiang University City College, Hangzhou 310015, China. fuxc@zucc.edu.cn
authors.forename: Xu-chun
authors.initials: XC
authors.lastname: Fu
authors.forename: Shu-yu
authors.initials: SY
authors.lastname: Zhan
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000502:physiology; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000502:physiology; D006801:Humans; D006860:Hydrogen Bonding; D007408:Intestinal Absorption; D008956:Models, Chemical; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012044:Regression Analysis
chemical_list: D000319:Adrenergic beta-Antagonists; D004364:Pharmaceutical Preparations