In Silico Quantitative Structure Pharmacokinetic Relationship Modeling on Antidiabetic Drugs: Half-Life

Author(s): Yash Paul, Parina, Aman Singla and Bhupinder Singh

An estimate of half-life (t1/2) is of paramount importance in assessing the efficacy of drugs used to treat diabetes in patients. This study was conducted to develop Quantitative Structure Pharmacokinetic Relationship (QSPkR) for the prediction of t1/2 in human for congeneric series of twenty 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 cross-validated coefficients (Q2) using LOO method (p<0.005). The overall predictability was found to be high half-life (t1/2) (R2 = 0.9354 F = 31.35, S2 = 46.9583, Q2 = 0.7860, p<0.005). Half-life (t1/2) in the present QSPkR investigations was found to depend upon geometrical and constitutional parameters. As lipophilic and electronic parameters were observed to be considerably significant, the biological half-life tends to be diffusional rate limited for antidiabetic drugs.

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