Pharmacokinetics of a Sustained-Release Product of Indomethacin in the Elderly

Abstract

The pharmacokinetics of indomethacin (Indo) was studied in 10 healthy elderly male volunteers (age 67–81 years) following the oral administration of a single 75-mg dose of a sustained release form of Indo. The total and free plasma and erythrocyte concentrations of Indo were determined by a specific high-pressure liquid chromatographic method. A maximum concentration (C_max) of 4.28 ± (SE) 0.43 μg/ml was reached after 1.85 ± 0.22 h. The area under the plasma concentration versus time curve (AUC) was 22.83 ± 2.70 μg ml-¹ h and the plasma elimination half-life was 4.34 ± 0.64 h. The maximum concentration of Indo in the red blood cells was 0.123 ± 0.013 μg/ml and was obtained at 1.95 ± 0.14 h after drug administration. The erythrocyte concentrations of Indo represented 2.4% of the total plasma levels of Indo whereas only 1.3% of the drug was unbound to plasma proteins. The C_max and AUC values determined in the elderly were approximately double the values reported in young adults for the same dose.

Differences in the pharmacological properties of rat and chicken brain fatty acid amidohydrolase

“…However, significant inhibition of FAAH is unlikely to be found in vivo after administration of a therapeutic dose of indomethacin, given that the peak plasma concentration (e.g. ∼12 μ M after administration of a 75 mg controlled release preparation to elderly volunteers, Bruguerolle et al ., 1986 ) is much lower than the K i value found here.…”

Cyclooxygenase‐2 Inhibitors Decrease Interleukin‐1β–Stimulated Prostaglandin E2 and IL‐6 Production by Human Gingival Fibroblasts

“…Peak plasma levels of rofecoxib after therapeutic doses of 12.5 to 50 mg can reach approximately 1 µM and can inhibit PGE 2 >90%. 76 Peak plasma concentrations of indomethacin range from approximately 3 µM to 12 µM for doses of 25, 50, or 75 mg, respectively, 77 and in this study we used from 1 to 500 µM indomethacin. Therefore, the experimental concentrations of the COX inhibitors studied in this work, which are used in humans, are similar to their plasma levels achieved in vivo.…”

Microglial responses to amyloid β peptide opsonization and indomethacin treatment

“…Indomethacin, at 1.0 μg/ml, and vehicle were also replenished at Days 3, 6, and 9 in the course of medium changes. The 1.0 μg/ml indomethacin concentration is at the upper end of the physiologically normal range achieved in blood after therapeutic doses of the drug [13], and was chosen to insure that any failure of indomethacin to affect chemotaxis to or phagocytosis of Aβ was not due to inadequate drug dosage. In some experiments, a 0.1 μg/ml concentration of indomethacin, which is at the lower end of the physiologically normal range achieved in blood after therapeutic doses, was included in order to evaluate effects at a lesser concentration.…”