OBJECTIVES: Distribution coefficient is used as a quantitative measure for assessing a drug molecule affinity for the biological membranes. Since bile acids are known for their function as modifiers of drug penetration across biological membranes, the aim of this study was to estimate the influence of cholic acid (CA) on the distribution coefficient of simvastatin (SV) which is a highly lipophilic compound with extremely low water-solubility and bioavailability. METHODS: Distribution coefficients and logD of SV with or without CA were measured by shake-flask method in n-octanol/buffer systems at pH 5 and pH 7.4. SV concentrations in aqueous phase were determined by HPLC-DAD. In order to analyse theoretically complexation of SV with CA, semi-empirical PM3 method implemented in MOPAC software package in the Chem3D Ultra program has been applied.  RESULTS: Upon addition of CA, statistically significant decrease of SV logD was observed at both selected pH values (from 4.70±0.01 to 4.41±0.13 at pH 5, and from 4.59±0.06 to 4.40±0.04 at pH 7.4). Analysing the molecular aggregates of SV with CA, it was observed that CA is bonded to SV by hydrophobic interactions, while OH groups are oriented towards the outer side of the aggregate. Hence, the formed aggregate is more hydrophilic than SV molecule alone. CONCLUSIONS: Our data indicate that CA decreases the values of SV distribution coefficient. This may be the result of the formation of hydrophilic complexes increasing the solubility of SV that could consequently lead to the increase of SV bioavailability. In order to confirm these results, further in vivo investigations of their interactions at molecular level need to be undertaken. Acknowledgement: This work is supported by Ministry of Education, Science and Technological Development of Serbia, Project III41012.