Quantitative relationships between structure and pharmacokinetic parameters using molecular connectivity chi indices...

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 (chi) 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 = 0.86), total body clearance (r = 0.89), and protein binding association constant (r = 0.78) for substituted 2-sulfapyridines were obtained. However, including the pKa (indicative of electronic effects) of the compounds within the equation as a predictor variable caused an increase in the correlation coefficients.