Abstract
Ibuprofen is a widely used and well-tolerated analgesic and antipyretic. It is
desirable to have a formulation with a rapid rate of absorption because it is
required for rapid pain relief and temperature reduction. Previous studies have
described the pharmacokinetic profiles of ibuprofen suppository and the mean
peak times of ibuprofen suppository were around 1.8 hours, indicating a
slower rate of absorption. The aim of this study is to compare the
pharmacokinetic parameters of rectal administration of ibuprofen between enema
and suppository form in order to provide evidence for the faster absorption
rates of ibuprofen enema. This study was a phase-1 clinical study, open-label,
randomized and two-way crossover with one-week washout period comparing the
absorption profile of equal dose of ibuprofen administered rectally in two
treatment phases: ibuprofen suppository and enema. Blood samples were collected
post dose for pharmacokinetic analyses. Tmax was analyzed using a
Wilcoxon matched paired test. A standard ANOVA model, appropriate for
bioequivalence studies was used and ratios of 90% confidence intervals
were calculated. This study showed that Tmax for ibuprofen enema was
less than half that of ibuprofen suppository (median 40 min vs.
90 min, respectively; p-value=0.0003). Cmax
and AUC0–12 for ibuprofen enema were bioequivalent to
ibuprofen suppository, as the ratio of
test/reference=104.52%, 90% CI
93.41–116.95% and the ratio of
test/reference=98.12%, 90%CI
93.34–103.16%, respectively, which fell within
80–125% bioequivalence limit. The overall extent of absorption
was similar to the both, which were all well tolerated. In terms of
Tmax, Ibuprofen enema was absorbed twice as quickly as from
ibuprofen suppository. Therefore it is expected that an ibuprofen enema may
provide faster onset of analgesic and antipyretic benefit.
Key words
enema - fever - ibuprofen - rectal
