title: Dual Incorporation of the in vitro Data (IC50) and in vivo (Cmax) Data for the Prediction of Area Under the Curve (AUC) for Statins using Regression Models Developed for Either Pravastatin or Simvastatin.
abstract: Linear regression models utilizing a single time point (Cmax) has been reported for pravastatin and simvastatin. A new model was developed for the prediction of AUC of statins that utilized the slopes of the above 2 models, with pharmacokinetic (Cmax) and a pharmacodynamic (IC50 value) components for the statins. The prediction of AUCs for various statins (pravastatin, atorvastatin, simvastatin and rosuvastatin) was carried out using the newly developed dual pharmacokinetic and pharmacodynamic model. Generally, the AUC predictions were contained within 0.5 to 2-fold difference of the observed AUC suggesting utility of the new models. The root mean square error predictions were<45% for the 2 models. On the basis of the present work, it is feasible to utilize both pharmacokinetic (Cmax) and pharmacodynamic (IC50) data for effectively predicting the AUC for statins. Such a new concept as described in the work may have utility in both drug discovery and development stages.
authors.affiliation: Suramus Bio, Drug Development, JP Nagar I Phase, Bangalore, Karnataka, India.
authors.forename: N R
authors.initials: NR
authors.lastname: Srinivas
mesh_terms: D019540:Area Under Curve; D000069059:Atorvastatin / Q000493:pharmacokinetics / Q000494:pharmacology; D015195:Drug Design; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D016014:Linear Models; D017035:Pravastatin / Q000493:pharmacokinetics / Q000494:pharmacology; D000068718:Rosuvastatin Calcium / Q000493:pharmacokinetics / Q000494:pharmacology; D019821:Simvastatin / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D019821:Simvastatin; D017035:Pravastatin