ABSTRACT
The pharmacokinetics of the anti-inflammatory agent fentiazac and its principal plasma metabolite, p-hydroxyfentiazac, have been investigated after repeated oral administration of fentiazac to male volunteers. Each volunteer received 200 mg of fentiazac twice daily for 15 d. Absorption was quite rapid, though some inter-subject variation in rates of absorption and bioavailability was observed. tmax values after the first dose ranged from 0.75-3 h while Cpmax values were 1050-4880 ng/ml. Elimination of fentiazac from plasma occurred rapidly in curvilinear fashion, so that concentrations were only 1% of their maximum value by 12 h after dosing. Maximum concentrations of p-hydroxyfentiazac after a single dose of fentiazac were 25.6-79.4% of those of fentiazac and were achieved at similar times. The metabolite was more slowly eliminated; the mean concentration of p-hydroxyfentiazac 12 h after a single dose was still 8% of its maximal value. On repeated administration, AUC0-12 h values for fentiazac and hydroxyfentiazac increased, as indicated by accumulation factors of 1.17 +/- 0.11 and 1.30 +/- 0.11 on days 8 and 15, respectively, for fentiazac and 1.72 +/- 0.15 and 1.77 +/- 0.10 for hydroxyfentiazac. There was no significant difference between days 8 and 15 in the extent of accumulation of either compound. Trough concentrations of fentiazac and hydroxyfentiazac on days 12 and 15 were similar to those on day 8. The clinical significance of these observations is discussed.