Ibuprofen blood plasma levels and onset of analgesia


  • Disclosures No funding was provided by any sponsor for this specific study, although Reckitt Benckiser Healthcare did originally fund the two studies analysed for time to onset. Donald R Mehlisch, MD, DDS (DM) has previously received fees for consultancy and independent research from Reckitt Benckiser Healthcare (and previously Boots Healthcare International Ltd.). John Sykes BSc, MSc, CStat (JS) is a statistical consultant for Reckitt Benckiser Healthcare.

Donald R. Mehlisch, MD, DDS Donald R Mehlisch & Associates, 339 Tomahawk Drive, Palm Desert, CA 92211, USA
Tel.: +1 760 345 0475
Fax: +1 760 345 0476
Email: dmehlisch@aol.com


Background:  Ibuprofen is widely available as an over-the-counter treatment for pain and fever. New formulations are now available, with varying pharmacokinetic profiles. However, few studies have been specifically designed to examine the relationship between ibuprofen plasma levels and onset of analgesia. This study aimed to determine a value, or range of values, for the blood plasma level of ibuprofen at which onset of analgesia could be expected.

Methods:  Placebo-controlled clinical trials, investigating the efficacy and pharmacokinetics of ibuprofen 200 mg and 400 mg, were identified. A retrospective posthoc analysis was performed on data from trials that incorporated time to perceived pain relief as an endpoint and the incidence of confirmed/unconfirmed perceptible pain relief was assessed. Mean ibuprofen blood plasma levels were computed at various time points using data from pharmacokinetic trials.

Results:  Two trials were identified with sufficient data to analyse time to onset of analgesia (Current Controlled Trials ISRCTN73768226, ISRCTN86009231). For 400 mg ibuprofen, the incidence of confirmed perceptible pain relief was significantly greater vs. placebo at 20 min post dosing (both studies). For 200 mg ibuprofen, significance was reached at 20 min (one study). In the 17 trials, with data on plasma concentrations for patients receiving 400 mg ibuprofen, the weighted mean value at 20 min post dosing was 8.4 μg/ml (95% confidence interval, 6.8–10.1).

Conclusions:  Results of this study provide useful information for the development of new ibuprofen formulations. Further prospective studies and studies using other endpoints to define efficacy and onset would be of interest.