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In Silico Quantitative Structure Pharmacokinetic Relationship Modelling on Quinolone Drugs: Time of Peak Plasma Concentration

Yash Paul, Avinash S. Dhake, Milind Parle and Bhupinder Singh

An estimate of time to reach maximum plasma concentration (tmax) is of paramount importance in assessing the efficacy of drugs used to treat acute conditions like pain and insomnia, which can be treated by a single dose. This study was conducted to develop Quantitative Structure Pharmacokinetic Relationship (QSPR) for the prediction of tmax in men for congeneric series of 24 quinolone drugs, using computer assisted Hansch approach. The QSPR correlations were duly analyzed using a battery of apt statistical procedures and validated using leave-one-out (LOO) approach. Analysis of several hundreds of QSPR correlations developed in this study revealed high degree of cross-validated coefficients (Q2) using LOO method (p<0.001). The overall predictability was found to be high (R2 = 0.9147 F=33.96 S2=0.0748, Q2=0.8046 p<0.001). Both logarithmic transform and inverse transform of the tmax value resulted in decrease in correlation coefficient (for Log tmax, R2= 0.8636 and for 1/tmax, R2= 0.8701). Topological and electrostatic parameters were found to primarily ascribe the variation in tmax. The results indicate the involvement of dissolution rate limited absorption rather than permeation limited, as hardly any dependence on Log P was observed.