Time-Dependent Influence of Diazepam on the Pharmacokinetics of Orally Administered Diclofenac Sodium in Human Subjects

Abstract

The influence of time of administration on the serum levels of diclofenac when administered alone and in combination with diazepam was studied in 8 healthy human volunteers. The peak serum levels (Cmax) of diclofenac were significantly (p < 0.05) higher (45%) and the mean residence time and apparent steady-state volume of distribution (Vss) were lower (23 and 26%, respectively) after drug administration at 1000h than after administration at 2200h. A significant rise in the mean Cmax of diclofenac when administered concomitantly with diazepam at both 1000h (68%) and 2200h (112%) was observed. In addition, it was interesting to note that diazepam altered pharmacokinetic parameters such as the area under the plasma concentration-time curve (60% increase), clearance (36% decrease) and Vss (24% decrease) of diclofenac to a significant extent (p < 0.05) after the combination treatment at 2200h only. This time-dependent prominence in the effects of diazepam on the pharmacokinetics of diclofenac may be because of the time-dependent effects of diazepam on the physiological functioning of the gastrointestinal tract.