Effects of food on pharmacokinetics of immediate release oral formulations of aspirin, dipyrone, paracetamol and NSAIDs - a systematic review

Abstract

Aims: It is common to advise that analgesics, and especially non-steroidal anti-inflammatory drugs (NSAIDs), be taken with food to reduce unwanted gastrointestinal adverse effects. The efficacy of single dose analgesics depends on producing high, early, plasma concentrations; food may interfere with this. This review sought evidence from single dose pharmacokinetic studies on the extent and timing of peak plasma concentrations of analgesic drugs in the fed and fasting states.

Methods: A systematic review of comparisons of oral analgesics in fed and fasting states published to October 2014 reporting kinetic parameters of bioavailability, time to maximum plasma concentration (tmax ), and its extent (Cmax ) was conducted. Delayed-release formulations were not included.

Results: Bioavailability was not different between fasted and fed states. Food typically delayed absorption for all drugs where the fasting tmax was less than 4 h. For the common analgesics (aspirin, diclofenac, ibuprofen, paracetamol) fed tmax was 1.30 to 2.80 times longer than fasted tmax . Cmax was typically reduced, with greater reduction seen with more rapid absorption (fed Cmax only 44-85% of the fasted Cmax for aspirin, diclofenac, ibuprofen and paracetamol).

Conclusion: There is evidence that high, early plasma concentrations produces better early pain relief, better overall pain relief, longer lasting pain relief and lower rates of remedication. Taking analgesics with food may make them less effective, resulting in greater population exposure. It may be time to rethink research priorities and advice to professionals, patients and the public.

Keywords: analgesic; bioavailability; food; maximum plasma concentration; oral; pharmacokinetic.

Figure 1

Flow chart of search results

Figure 2

AUC for fasting and fed states assessed over longest time reported (all drugs). A logarithmic scale is used because of the wide range of AUC values. The inset scale indicates the number of participants in each comparison

Figure 3

t_max in fed and fasted state for individual drugs. The inset scale indicates the number of participants in each comparison. Blue symbols are fast-acting formulations of diclofenac potassium, ibuprofen lysine, naproxen sodium and paracetamol plus bicarbonate

Figure 4

C_max in fed and fasted state for individual drugs. The inset scale indicates the number of participants in each comparison. Blue symbols are fast-acting formulations of diclofenac potassium, ibuprofen lysine, naproxen sodium and paracetamol plus bicarbonate. Note that only data with t_max when fasting of less than 4 h are shown

Figure 5

Relationship between A) C_max for doses of 200 mg and 400 mg ibuprofen in standard acid and fast acting formulations and observed NNT (equation to regression line –0.031 × + 3.1 (r² = 0.74)) and B) observed remedication rate (equation to regression line –1.0 × + 74 (r² = 0.79)). Calculated using data from ss. Weighted mean C_max values were multiplied by dose to obtain C_max values; NNT and percentage remedicating values were taken from tables or text