Pharmacokinetics of intraarticular indomethacin in patients with osteoarthritis

Summary The pharmacokinetics of intraarticular indomethacin was evaluated in 10 patients with osteoarthritis in an open labelled, randomized, cross-over study. Each patient received a single dose of 10 mg indomethacin by the intraarticular and the intravenous routes with a seven-day interval between the injections. Blood was repeatedly collected and urine was collected for 24 h after dosing.Indomethacin was rapidly absorbed from the joint, giving a maximum serum concentration (C_max) of 0.60 g · ml^–1 approximately 1 h after dosing. The systemic bioavailability (f) was 80% and the mean absorption time (MAT) was about 2 h. The apparent terminal half-life and mean residence time (MRT) were 2.8 h and 4 h, respectively. The urinary recovery of total indomethacin (unchanged + glucuronides) was 24% of the dose and renal clearance (CL_R) was estimated to be about 21 ml · min^–1. The disposition of indomethacin after intravenous and intraarticular administration appeared to be similar.The results suggest that the intraarticular administration of indomethacin would not exclude the risk of developing untoward, systemic, concentration-dependent effects.