Time-Dependent Influence of Diazepam on the Pharmacokinetics of Orally Administered Diclofenac Sodium in Human Subjects
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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.
KeywordsDiazepam Ketorolac Drug Invest Sulindac Mean Residence Time
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