Vol. 2, Issue 3 (2017)
In silico quantitative structure pharmacokinetic relationship modeling on cardiovascular Drugs: Serum protein binding
Author(s): Chouhan Jagtar Singh, Jat Rakesh Kumar, Paul Yash
Abstract: An estimate of serum protein binding (%SPB) is of paramount importance in assessing the efficacy of drugs used to treat acute conditions like hypertension, arrhythmias. This study was conducted to develop Quantitative Structure Pharmacokinetic Relationship (QSPKR) for the prediction of %SPB in men for congeneric series of eighteen cardiovascular derivatives, 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<0.001). The overall predictability was found to be high % SPB (R2=0.9673 F=226.38.31 S2=2.25, Q2=0.9274 p<0.001). %SPB in the present QSPKR investigations was found to depend upon electrostatic, constitutional and topological etc. Its positive dependence on such parameters indicates that hydrogen bonding and van der Waals’ interactions play a stellar role in governing protein binding. %SPB does not seem to have any dependence on lipophilic and electronic parameters indicating that the hydrophobic and ionic bonding of cardiovascular is negligible.