Pharmacokinetics of chlormezanone in healthy volunteers

The kinetics of chlormezanone were determined after oral administration of single (400 mg) and multiple doses (400 mg/day during 8 days) in eight young healthy male subjects. Plasma levels determination had been carried out by HPLC. After single dose administration, Cmax concentrations 4.62 +/- 0.75 mg/l were obtained (Tmax) 2.18 +/- 1.49 h after drug intake. Area under plasma concentrations time curve was 224.93 +/- 27.79 mg.h/l and terminal half-life 40.50 +/- 4.19 h. On chronic regimen, chlormezanone accumulates in the body: trough plasma concentrations are significantly increased from Day 7 (2.97 +/- 0.45 mg/l) to Day 9 (5.41 +/- 0.90 mg/l) and reach the steady state faster than it can be expected from half-life (40 hours) and dosing interval (24 hours). Elimination is faster (T1/2 beta = 37.14 +/- 3.18 h) after chronic regimen. Area under curve during dosing interval at steady state (164.19 +/- 21.70 mg.h/l) is significantly lower than the area under curve between zero and infinity in the single dose sequence (224.93 +/- 27.79 mg.h/l). These results agree with probable induction effect of chlormezanone on its own metabolism.