A comparative bioavailability study of two ibuprofen formulations after
single-dose administration in healthy volunteers
Metta Sinta Sari Wiria, Fransiscus D. Suyatna
Ibuprofen (2-(4-isobutylphenyl)-propionic acid, C13 H18 O2 ) is a non-steroidal antiinflamatory drug. It is a racemate of (S)-(+) dan (R)-(-) enantiomer with the ratio 1:1, but only the S-enantiomer is active. Both enantiomers posses the same pharmacokinetic (concentration vs. time) profile. The analgesic and antiinflamatory effect of the drug have been used clinically to treat post operative pain in young adults and children with minor side effect. The main side effect of ibuprofen is gastro-intestinal tract irritation e.g., gastritis. The mechanism of antiinflamation of ibuprofen is through the inhibition
of the prostaglandin and leukotriene biosynthesis. Ibuprofen is rapidly absorbed after oral administration
in men, and peak plasma concentration is observed after 1 to 2 hours. The half-life in plasma is about 2
hours. Although the rectal preparation may have some delay in reaching the peak plasma concentration,
ibuprofen suppositories are absorbed efficiently. The
peak plasma concentration (Cmax) is about 5-20 mg/L
(oral, single dose of 200 mg) or about 12.4-30.1 mg/L (suppository, doses of 20 mg/kg BB). The bioavailability
of suppository formulation is about 73%. Ibuprofen is extensively bound to plasma proteins (90-
99%), penetrates slowly from plasma to synovial spaces and may accumulate there in higher con-
centration. The drug is metabolized by hydroxylation and carboxylation to form two inactive metabolites,
which are eliminated after conjugation to glucuronic acid. The excretion of ibuprofen is rapid and complete;
more than 90% of an ingested dose is excreted in the urine as metabolites or their conjugates, and no
ibuprofen is found in the urine.1,2,5
The bioavailability of two (or more) formulations of the same active ingredient could differ from one to the
other; therefore bioequivalence studies become the important part of registration dossiers. If they are
equivalent, then one may subsequently claim that the therapeutic efficacy of both formulations is similar. It
may also mean that the beneficial and side effects of the two drugs are identical, and hence the formulations
are interchangeable.
The aim of this study was to compare, the pharmacokinetic profiles and to evaluate the bioequivalence of two
formulation of 125 mg ibuprofen suppositories (Ibukal® from PT.Kalbe Farma Tbk., Jakarta and Proris® from
PT. Pharos Indonesia, Jakarta), after single dose rectal administration in healthy volunteers of both sexes.
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