COMPARISON OF THE EFFECTS OF CIMETIDINE AND DIAZEPAM ON THE PHARMACOKINETICS OF PARACETAMOL IN HEALTHY HUMAN VOLUNTEERS

COMPARISON OF THE EFFECTS OF CIMETIDINE AND DIAZEPAM ON THE PHARMACOKINETICS OF PARACETAMOL IN HEALTHY HUMAN VOLUNTEERS

ABSTRACT

The influence of Cimetidine (400 mg) and Diazepam (5 mg) on the pharmacokinetics of oral paracetamol (1000 mg) was studied and compared in eight (8) healthy human under two (2) protocols; concomitant and delayed administration of paracetamol. Subjects received one treatment at each of the five sessions with a 2 weeks wash out period in-between. Paracetamol alone was used as control. This was compared with concomitant administration with Cimetidine and then delayed (l hour later) administration of paracetamol after Cimetidine. Diazepam was used in phase IV and V under the same protocol of concomitant administration with paracetamol and delayed administration of paracetamol l hour of diazepam. Ultraviolet spectrophotometer was used to determine the saliva concentration of paracetamol. Pharmacokinetic parameters (Kab, t1/2el, t1/2(ab), Kel, Kab, lag time were determined by plotting paracetamol concentrations against time on a logarithmic scale while other parameters were calculated. There was no significant effect (p > 0.05) on the parameters on concomiittant administration for both drugs (cimetidine and diazepam) when compared to the control. However, on delayed administration of paracetamol 1 hour after administration of diazepam, Tmax and lag time were greatly reduced 31.11 % and 50 % repectively P < 0.05. T1/2(ab) and Kel were significantly increased 48.42 % and 54.57 % P < 0.05 respectively. The volume of distribution (Vd) and clearance (Cl) were not significantly affected P > 0.05. Delayed administration of paracetamol 1 hour after cimetidine affected all the parameters Cmax and Kab were significantly reduced P < 0.05 by 30.02 % and vii 45.06 % respectively. While Tmax, t1/2(ab) and lag time were significant increased (p < 0.05) by 47.97 %, 42.32 % and 60.13 % respectively. Clearance (Cl) and Kel were reduced significantly (P < 0.05) by 20.75 % and 42,76 % respectively. T1/2(el) and AUC0 - ∞ were increased by 39.20 % and 29.08 % respectively. The above findings show that concomitant administration of paracetamol + diazepam and of paracetamol + cimetidine does not cause any effect on the kinetics of paracetamol. On the other hand, delayed administrations of paracetamol one hour after cimetidine show decrease in absorption and delayed elimination probably due to delay in gastric emptying and inhibition of metabolism respectively. Administration of paracetamol one hour after diazepam ingestion shows increase in absorption and change in other pharmacokinetic parameters due to enhanced gastric emptying and amplitude of contraction.

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