The aim of the presented study was to look for a relationship between physicochemical parameters of selected drugs and the value of between-subject variability of area under the curve (AUCBSV). The analysis was performed for a group of 100 drugs prescribed in different disease entities in humans. At first, a direct correlation between 52 physicochemical parameters and AUCBSV was determined. In the next step, physicochemical parameters of the drugs calculated in silico were divided into quintile groups and a search for the correlation between the AUCBSV values for individual parameters in each quintile group and the number of the quintile was conducted. Only in case of 5 of the 52 parameters analyzed (partition coefficient octanol/water - XLogP, ionization potential - IP, globularity - Glob, polarizability - α, and polar surface area - PSA), it was possible to create an arithmetic expression $$ [(X\log P + {\text{IP}} + {\text{Glob}})^{{{\text{Log}}\alpha}} - {\text{PSA}}] $$ , for which the correlation with AUCBSV value was statistically significant (P < 0.05). Results of this study indicate that XLogP, α, IP, Glob, and PSA are a group of physicochemical parameters related to AUCBSV.