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COMPARISON OF THE EFFECTS OF CIMETIDINE AND TRAMADOL ON THE DISPOSITION OF PARACETAMOL IN HEALTHY HUMAN VOLUNTEERS

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  • Reference Style: APA
  • Recommended for : Student Researchers
  • NGN 3000

ABSTRACT

The influence of cimetidine (400mg) and Tramadol (100mg) on the disposition of oral single dose (1g) Paracetamol was studied and compared in 8 healthy human volunteers under two protocols; concomitant and delayed paracetamol administration. Subjects received one treatment at each of five sessions 2wk apart. Ingestion of Paracetamol (1g) alone was used as control and compared with paracetamol concentration on concomitant (with tramadol (100mg) and then cimetidine (1g)) and delayed administration (1h 45mins after tramadol and 1h after cimetidine). Saliva paracetamol concentrations were determined with UV-Spectrophotometer. Pharmacokinetic parameters (kab, t1/2ab, kel, t1/2el and lag time), were determined by plotting paracetamol concentrations against time on a logarithmic scale while other parameters were calculated. For the influence of cimetidine and tramadol on paracetamol when either of the drugs was administered concomitantly with the paracetamol there were no significant changes (P>0.05) when compared to the control. On delayed administration of paracetamol 1h 45mins after tramadol however, Tmax and t1/2ab were significantly (P0.05). Delayed administration of paracetamol 1hour after cimetidine on the other hand affected all the pharmacokinetic parameters significantly. The (Cmax) and kab were significantly reduced (P<0.05) by 31.38% and 50.24% respectively, while Tmax, t 1 /2ab and lag-time were significantly increased (P<0.05) by 45.65%, 46.65% and vii 36.41% respectively. The t1 /2el and AUCo-∞ were also significantly increased (P<0.50) by 59.31% and 29.45% respectively. Clearance (cl) and kel on the other hand were significantly reduced (P<0.050) by 21.90% and 59.74% respectively. The volume of distribution (vd) was significantly increased by 47.30%. These findings indicated that cimetidine and tramadol do not affect the pharmacokinetics of paracetamol when either drug was taken concomitantly with paracetamol. However, when paracetamol is administered 1h 45mins after tramadol (100mg), there was a significant delay in the absorption of paracetamol, but the elimination is not significantly affected. There is both impaired absorption and inhibited metabolism of paracetamol when the administration was delayed 1 hour after cimetidine.




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