The aim of this investigation was to evaluate the in vivo potential of poly(amidoamine) dendrimers (PAMAM) based simvastatin (SMV) formulations as nanoscale drug delivery units for controlled release action of simvastatin. Drug-dendrimer complexes were prepared and characterized by Fourier transform infrared (FTIR) spectroscopy. In a pharmacodynamic study, the percent increase in cholesterol was less with PAMAM dendrimer formulations as compared to pure drug. The cholesterol level was increased to 20.92% with pure SMV, whereas it was 11.66% with amine dendrimer, 11.49% with PEGylated dendrimer, and 10.86% with hydroxyl dendrimer formulations. Reduction in the increase in triglyceride and low density lipoprotein level was also more prominent with the drug-dendrimer formulations. The order of increase in high density lipoprotein level was PEGylated PAMAM-SMV (4.04%) > PAMAM-amine-SMV (2.57%) > PAMAM-hydroxyl-SMV (1.48%) > pure SMV (1.09%). Dendrimer-SMV formulations showed better pharmacokinetic performances than pure SMV suspension. The peak plasma SMV concentration increased from 2.3 μg/mL with pure SMV to 3.8 μg/mL with dendrimer formulations. The dendrimer mediated formulation had 3-5 times more mean SMV residence time than pure SMV. Furthermore, SMV absorption and elimination rates were decreased significantly, showing controlled release of SMV from the dendrimer formulations.