Aims: The pharmacokinetics and safety profile of JTE-522, 4-(4-cyclohexyl-2 methyloxazol-5-yl)-2-fluorobenzensulphonamide, a novel selective cyclooxygenase-2 inhibitor were investigated in healthy male volunteers. Methods: Initially, as a pilot study, five groups of two subjects were given oral doses of 3-100 mg of JTE-522. After safety assessment, subjects were given 150 and 200 mg of JTE-522. The effect of food-intake on the pharmacokinetics of JTE-522 at a dose of 150 mg was examined. In the multiple-dose study, subjects were given 150 mg of JTE-522 once a day for 7 days. Concentrations of unchanged JTE-522 in plasma, blood and urine were determined by high performance liquid chromatography (h.p.l.c.). Concentrations of metabolites were estimated with h.p.l.c. chromatograms and calibration curves for quantification of unchanged JTE-522. Results: In the course of this study, no serious abnormality attributable to the test drug was observed, suggesting that JTE-522 was well tolerated in healthy subjects. In a single-dose study, the concentrations of JTE-522 in blood were much higher than the corresponding concentrations in plasma. JTE-522 was readily distributed to blood cells and percentage distribution into blood cells was more than 99.0%. However, the values of Cmax in blood at doses of 100, 150, 200 mg JTE-522 were 15241, 20445 ± 3918 (16333-24556), 20965 ± 3260 (17544-24386) ng ml-1, respectively. These findings suggest that JTE-522 has a high affinity for blood cells and the distribution into blood cells is limited at the higher doses of over 100 mg. In a multiple dose study, pharmacokinetic parameters including t1/2 and AUC after the fourth administration were comparable with that of the seventh administration. Thus, these findings suggest the absence of accumulation on the multiple-dosing of JTE-522. Conclusions: These results indicate that JTE-522 has an acceptable pharmacokinetic profile for clinical use without any serious adverse events as we verified in healthy young male volunteers.
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