The main objective of this study was to develop a pharmacokinetic-pharmacodynamic (PK/PD) model for the analgesic effect of ibuprofen and flurbiprofen using subjective as well as objective parameters. Serum concentrations of the individual enantiomers after oral administration of racemic ibuprofen (400 mg) and flurbiprofen (100 mg) were monitored using reversed phase HPLC. The pharmacokinetic data of the S-enantiomer was linked to the effect data using a hypothetical effect compartment. The effect data were fitted to Emax model. PK/PD analysis were performed using both objective (evoked potentials) and subjective (pain intensity scale) parameters. Concentrations of S-ibuprofen were found to be consistently larger than of R-ibuprofen and differed in various pharmacokinetic parameters after oral administration of racemic ibuprofen. Pharmacokinetic parameters of the enantiomers of flurbiprofen, such as volume of administration and clearance, also differed. Comparison of cumulative effects calculated as the area under the effect-time curve (AUCE) showed a statistically significant difference from placebo for both ibuprofen and flurbiprofen using evoked potential values. However, using pain rating values ibuprofen AUCE did not differ statistically significant from placebo whereas flurbiprofen AUCE did. PK/PD modeling of both evoked potentials and pain rating data than in evoked potential data. Hence, EP monitoring may allow to evaluate analgesic activity with a smaller number of subjects than pain rating.