The influence of food and repeated dosing on the bioavailability of indomethacin from a multiple-units...

A concomitant meal did not affect the extent of bioavailability of indomethacin from a multiple-units controlled-release capsule formulation containing enteric-coated pellets, but the presence of food delayed absorption. When a capsule containing 75 mg indomethacin was administered after a 12 h fast, the mean peak drug concentrations in plasma of 2.7 micrograms/ml +/- 0.8 SD occurred at a mean time of 4.2 h (range 2-6 h). When this dose was administered with a substantial breakfast, the mean of the peak plasma concentration of 2.2 micrograms/ml +/- 1.0 SD occurred at 6.4 h (range 5-12 h). Secondary peak plasma drug concentrations, occurring at approximately 14 h after dosing, were more prominent and the times to reach the second peak more variable when the capsules were administered with food. Drug bioavailability after co-administration with food was 91% of that following administration after fasting. When the controlled-release capsule was administered during 3 days in a b.i.d. dosage regimen, drug bioavailability was 103% of that from a standard capsule administered q.i.d. The mean peak level after administration of the last dose of 50 mg as controlled-release capsules was 2.5 micrograms/ml +/- 1.1 SD and the means of peak levels after the penultimate and last doses of 25 mg as standard capsules were 2.0 micrograms/ml +/- 0.3 SD and 2.1 micrograms/ml +/- 0.7 SD, respectively. The controlled-release capsule formulation was a reliable and reproducible source of indomethacin when administered as repeated doses or with food.