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Quantitative relationships between structure and pharmacokinetic parameters using molecular connectivity Chi indices I: Substituted 2-sulfapyridines

✍ Scribed by K. Reed; K. Mereish; B. Jensen


Publisher
John Wiley and Sons
Year
1984
Tongue
English
Weight
499 KB
Volume
73
Category
Article
ISSN
0022-3549

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✦ Synopsis


Quantitative relationships between the structure and pharmacokinetic parameters of several compounds have been derived using the molecular connectivity approach. The correlation coefficients of equations obtained using the Chi indices (x) as predictor parameters were compared favorably with those obtained by the linear free energy approach, where physicochemical parameters have been used as predictor variables. High correlation coefficients ( r ) for the first-order elimination rate constant ( r = 0.861, total body clearance ( r = 0.89), and protein binding association constant ( r = 0.78) for substituted 2-sulfapyridines were obtained. However, including the pK, (indicative of electronic effects) of the compounds within the equation as a predictor variable caused an increase in the correlation coefficients.

Keyphrases

Molecular connectivity-Chi indices, use in quantitative structure-pharmacokinetic relationships, substituted 2-sulfapyridines 0 Pharmacokinetic parameters-quantitative relationship to structure, determination by molecular connectivity Chi indices, substituted 2sulfapyridines Quantitative structure-pharmacokinetic relationships-application of molecular connectivity Chi indices, substituted 2-sulfapyridines ~~ ~ (I Ref. 11. Ref. 12. Ref. 13. Ref. 14. @ Permeability coefficient. 'Cumulative biliary excretion. Y Correlation coefficient of equations in which the log of the rharmacokinetic parameters are correlated with physicochemical properties. Correlation coefficient of equations in which the log of the pharmacokinetic parameters are correlated with x indices. l Correlatlon coefficient in whlch the antilogs of pharmacokinetic parameters are correlated with x indices. 1 Ref. 4. Ref. 3.