Parina Gill, Vivek Gill, Neeraj Singh & Nisha
An estimate of time to reach peak plasma concentration (tmax) is of paramount importance in estimating thr rate of absorption and efficacy of drugs to treat acute conditions viz. polyphasia, polydispia and fatigue to treat diabetes in patients. This study was conducted to develop Quantitative Structure Pharmacokinetic Relationship (QSPkR) for the prediction of tmax in human for congeneric series of seventeen antidiabetic drugs, using computer assisted Hansch approach. The QSPkR correlations were duly analyzed using a battery of apt statistical procedures and validated using leave-one-out (LOO) approach. Analysis of several hundreds of QSPkR correlations developed in this study revealed high degree of crossvalidated coefficients (Q2) using LOO method (p<0.005). The overall predictability for time to reach peak plasma concentration was found to be high (R2=0.9325, F=30.41, S2=0.1253, Q2=0.8502, p<0.005). The value of tmax of all drugs was found to depend upon various constitutional, topological and electrostatic parameters. Logarithmic transformation of the tmax value resulted in increase in correlation coefficient (R2=0.9751, F=65.19, S2=0.0016, Q2=0.9411, p<0.005).
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