TIME-DEPENDENT INFLUENCE OF DIAZEPAM ON THE PHARMACOKINETICS OF ORALLY-ADMINISTERED DICLOFENAC SODIUM IN HUMAN-SUBJECTS

The influence of time of administration on the serum levels of diclofe nac when administered alone and in combination with diazepam was studi ed in 8 healthy human volunteers. The peak serum levels (C-max of dicl ofenac were significantly (p < 0.05) higher (45%) and the mean residen ce time and apparent steady-state volume of distribution (V-ss) were l ower (23 and 26%, respectively) after drug administration at 1000h tha n after administration at 2200h. A significant rise in the mean C-max of diclofenac when administered concomitantly with diazepam at both 10 00h (68%) and 2200h (112%) was observed. In addition, it was interesti ng to note that diazepam altered pharmacokinetic parameters such as th e area under the plasma concentration-time curve (60% increase), clear ance (36% decrease) and V-ss (24% decrease) of diclofenac to a signifi cant extent (p < 0.05) after the combination treatment at 2200h only. This time-dependent prominence in the effects of diazepam on the pharm acokinetics of diclofenac may be because of the time-dependent effects of diazepam on the physiological functioning of the gastrointestinal tract.