In their recently published analysis, Moore and colleagues have analyzed available data concerning pharmacokinetic properties of oral analgesics under fed and fastened conditions 1. They debated whether the advice to take analgesics with a meal to prevent gastrointestinal discomfort and complications is still valid, since analgesic efficacy is superior on an empty stomach.
Although this conclusion is well-founded under certain conditions, we raise the question whether it is transferable to ‘real life’ conditions. The conclusion that fast release ibuprofen products act faster and better than ibuprofen acid analgesics is based on a few number of investigations in the dental surgery pain model (five studies cited in Moore et al. 2 where ‘time to meaningful pain relief’ was reported). Fast release formulations were observed to provide meaningful pain relief earlier compared with standard ibuprofen (see references in 2.
Elective dental surgery is performed under fasting conditions. In every day life, pain cannot be planned and, therefore, cannot be treated after a 10 h fast. How do fast releasing ibuprofen analgesics perform under such conditions?
We have identified two randomized, controlled trials investigating the effects of 400 mg ibuprofen in fast release formulation, 400 mg ibuprofen acid and placebo on episodic tension type headache.
In one study 3 in 200 patients the primary endpoint (‘time-weighted sum of pain relief rating and pain intensity difference from 0–3 h (SPRID 0-3) for ibuprofen sodium vs. placebo tablet’) was missed (P = 0.299).
In the second study 4 the primary endpoint was reached, but ‘pain intensity difference (PID)’ at 1, 2 and 3 h after intake was not different for the two ibuprofen formulations (P values of 0.651, 0.669 and 0.396, respectively).
Thus, under every day conditions, the fast releasing analgesic formulations might be not as advantageous as the highly controlled elective dental surgery pain model might suggest. It can be speculated that following other avenues might be more promising to provide patients with more effective, well tolerated analgesics. One well-proven approach is to combine analgesic compounds with complementary modes of action, e. g. ibuprofen and paracetamol 5 or NSAIDs with caffeine 6.
Competing Interests
There are no competing interests to declare.
References
- Moore RA, Derry S, Wiffen PJ, Straube S. Effects of food on pharmacokinetics of immediate release oral formulations of aspirin, dipyrone, paracetamol, and NSAIDs - systematic review. Br J Clin Pharmacol. 2015 doi: 10.1111/bcp.12628. . doi: 10.1111/bcp.12628. [Epub ahead of print] [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore RA, Derry S, Straube S, Ireson-Paine J, Wiffen PJ. Faster, higher, stronger? Evidence for formulation and efficacy for ibuprofen in acute pain. Pain. 2014;155:14–21. doi: 10.1016/j.pain.2013.08.013. . doi: 10.1016/j.pain.2013.08.013. [Epub ahead of print] [DOI] [PubMed] [Google Scholar]
- Study Evaluating A Novel Ibuprofen Formulation In Episodic Tension-Type Headache ClinicalTrials.gov; Available at https://www.clinicaltrials.gov/ct2/results?term=NCT01077973&Search= Search (last accessed 15 June 2015)
- Ibuprofen Sodium Tension Headache Study ClinicalTrials.gov; Available at https://www.clinicaltrials.gov/ct2/results?term=NCT01362491&Search= Search (last accessed 15 June 2015)
- Mehlisch DR, Aspley S, Daniels SE, Southerden KA, Christensen KS. A single-tablet fixed-dose combination of racemic ibuprofen/paracetamol in the management of moderate to severe postoperative dental pain in adult and adolescent patients: a multicentre, two-stage, randomized, double-blind, parallel-group, placebo-controlled, factorial study. Clin Ther. 2010;32:1033–49. doi: 10.1016/j.clinthera.2010.06.002. . doi: 10.1016/j.clinthera.2010.06.002. [DOI] [PubMed] [Google Scholar]
- Derry CJ, Derry S, Moore RA. Caffeine as an analgesic adjuvant for acute pain in adults. Cochrane Database Syst Rev. 2014;12 doi: 10.1002/14651858.CD009281.pub3. : CD009281. doi: 10.1002/14651858.CD009281.pub3. [DOI] [PMC free article] [PubMed] [Google Scholar]