The pharmacokinetics of pirazolac in human subjects.

Pirazolac (PAA) is a new non-steroidal anti-inflammatory drug (NSAID) belonging to the subgroup of heterocyclic acetic acids. PAA is rapidly and completely absorbed and bioavailable at all dose levels tested. Plasma level curves after oral administration of capsule-shaped tablets were no different from those after administration of a crystalline suspension. The drug is highly (greater than 99%) bound to plasma albumins and penetrates easily into the synovial fluid. Plasma levels obey first-order pharmacokinetics over the whole therapeutic dose range. PAA is entirely conjugated with glucuronic acid before leaving the body, mainly in the urine. It has an intermediate elimination half-life of 17 h which does not depend on age or sex. Under twice-daily administration, fairly constant plasma levels are achieved, thus avoiding the high fluctuation observed with short half-life NSAIDs like indomethacin or diclofenac, and also avoiding the excessive accumulation observed with long half-life NSAIDs like pyrazolones and oxicams. This pharmacokinetic property makes pirazolac highly appropriate for long-term therapy of rheumatic diseases.