Oral indomethacin has excellent bioavailability. Peak concentrations occur 1-2 hours after dosing (Table 26-1). Indomethacin is 90% bound to plasma proteins and tissues. The concentration of the drug in the CSF is low, but its concentration in synovial fluid is equal to that in plasma within 5 hours of administration.
Between 10% and 20% of indomethacin is excreted unchanged in the urine, partly by tubular secretion. The majority is converted to inactive metabolites, including those formed by O-demethylation (~50%), conjugation with glucuronic acid (~10%), and N-deacylation. Free and conjugated metabolites are eliminated in the urine, bile, and feces. There is enterohepatic cycling of the conjugates and probably of indomethacin itself. The t122 in plasma is variable, perhaps because of enterohepatic cycling, but averages 2.5 hours.
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