PHARMACOKINETICS AND EFFICACY OF LOW-DOSE KETOPROFEN IN POSTOPERATIVEDENTAL PAIN

A double-blind, randomised trial was carried out to investigate the re lationship between efficacy and various pharmacokinetic variables afte r single doses of racemic ketoprofen 12.5 and 25mg in patients with po stoperative pain after third molar surgery over a 4-hour investigation period. Serial venous blood samples were obtained at 0, 0.25, 0.5, 0. 75, 1, 1.5, 2, 3 and 4 hours after administration for subsequent deter mination of R(-) and S(+) ketoprofen. The relationship between the R(- ) and S(+) ketoprofen concentrations and pain experience was summarise d for each patient by the slope of the regression line for that indivi dual. There was no significant difference (p > 0.05) between the two d oses of ketoprofen for any of the efficacy measures. Peak plasma conce ntrations of both R(-) and S(+) ketoprofen were observed between 60 an d 90 minutes after dosage. A significant negative correlation (p < 0.0 02) was observed between the decrease in pain scores and plasma concen trations of both R(-) and S(+) ketoprofen after each dose. However, th e amount of variability in each patient's response makes it difficult to identify a causal relationship between these parameters. Low doses of ketoprofen provide satisfactory pain relief in the early postoperat ive period after third molar surgery. Efficacy of this analgesic does not appear to be dose related or directly related to plasma concentrat ions of either R(-) or S(+) enantiomers.