Faster, higher, stronger? Evidence for formulation and efficacy for ibuprofen in acute pain.
Moore RA., Derry S., Straube S., Ireson-Paine J., Wiffen PJ.
A Cochrane review of ibuprofen in acute pain suggested that rapidly absorbed formulations of salts, or features to speed absorption, provided better analgesia than standard ibuprofen as the free acid. We examined several lines of evidence to investigate what benefit derived from fast-acting formulations. A systematic review of the kinetics of oral ibuprofen (30 studies, 1015 subjects) showed that median maximum plasma concentrations of fast-acting formulations occurred before 50 min (29-35 min for arginine, lysine, and sodium salts) compared with 90 min for standard formulations. An updated analysis of clinical trials (over 10,000 patients) showed that fast-acting formulations produced significantly better analgesia over 6h and fewer remedications than standard formulations in both indirect and direct comparisons. In dental studies, 200-mg fast-acting ibuprofen (number needed to treat 2.1; 95% confidence interval 1.9-2.4) was as effective as 400 mg standard ibuprofen (number needed to treat 2.4; 95% confidence interval 2.2-2.5), with faster onset of analgesia. Individual patient data analysis in dental pain demonstrated a strong correlation between more rapid reduction of pain intensity over 0-60 min and better pain relief over 0-6h. Rapid initial reduction of pain intensity was also linked with reduced need for remedication. Fast-acting formulations of ibuprofen demonstrated more rapid absorption, faster initial pain reduction, good overall analgesia in more patients at the same dose, and probably longer-lasting analgesia, but with no higher rate of patients reporting adverse events. Achieving a better analgesic effect with fast-acting nonsteroidal anti-inflammatory drug formulations has important implications for safety. Formulation chemistry is of potential importance for analgesics.