Plasma and urine concentrations of 2-(3-chloro-4[3-pyrrolinyl]phenyl) propionic acid, pirprofen, a new nonsteroidal anti-inflammatory compound, are described for normal male volunteers receiving one or more doses of the drug. Orally administered pirprofen is rapidly and almost completely absorbed from the gastrointestinal tract, resulting in maximum plasma levels in 1 to 2 hr. Mean peak levels are 23 microng/ml after an oral pirprofen dose of 200 mg; lower doses given proportionally lower levels. Administration 1 hr after a meal slightly delays the peak plasma level, but the extent of absorption is not affected significantly. Administration of pirprofen, 150 mg, 4 times daily, or 200 mg, 3 times daily, results in nearly identical plasma levels at steady-state. Pirprofen has an apparent elimination half-life of about 7 hr. The results obtained from a 200-mg pirprofen-14C dose indicate that excretion of the drug occurs primarily by the renal route in the form of metabolites and is essentially complete within 24 hr. In urine, less than 5% of the administered dose is accounted for as unchanged drug.

Pirprofen was compared to placebo in a double-blind crossover study in 12 rheumatoid arthritis patients. Two approaches--univariate and multivariate--were used to analyze the study results which were in the form of arithmetic changes from pretreatment levels of six efficacy measurements. The univariate analysis failed to permit a single decision to be made regarding the further investigation and use of pirprofen in rheumatoid arthritis. However, the multivariate analysis which treats the efficacy variables simultaneously showed a clear differentation from placebo. Thus, multivariate analysis enabled the clinical pharmacologist to evaluate the new therapeutic agent in a complete and comprehensive manner. It allowed for a single decision to be made regarding the merits of pirprofen compared to placebo.