The effect of tenidap, a new nonsteroidal anti-inflammatory agent, on the pharmacokinetics and pharmacodynamics of prednisolone was studied in healthy male subjects. In a randomized crossover study, 12 subjects received either tenidap sodium 120 mg daily or placebo orally for 28 days. On day 21, each subject received a single dose of either 0.8 mg/kg oral prednisone or 0.66 mg/kg intravenous prednisolone followed by the other steroid on day 28. Blood and urine samples were collected, and the pharmacokinetic parameters of prednisone and prednisolone were determined in each treatment period. Pretreatment with tenidap did not cause any significant changes in the overall disposition of prednisone or prednisolone. For example, for free prednisolone, the intravenous area under concentration was 1,144 +/- 195 ng.h/mL and 1,244 +/- 140 ng.h/mL, and the systemic availability after oral prednisone was 53 +/- 10% and 51 +/- 12% with placebo and tenidap, respectively. The renal clearance of prednisolone was significantly reduced after tenidap pretreatment, however (from 143 to 77 mL/min/1.73 m2). The suppression of plasma cortisol and whole blood histamine levels were analyzed to evaluate the potential pharmacodynamic interactions between tenidap and prednisolone. There were no significant changes in the pharmacodynamic parameters between placebo and tenidap groups. The excretion of less than 20% of the dose of prednisolone in urine makes the overall effects of tenidap on prednisolone kinetics and dynamics of inconsequential clinical importance.