COMPARISON OF THE EFFECT OF A SINGLE ORAL DOSE OF CIMETIDINE AND PROPANTHELINE ON THE PHARMACOKINETIC OF PARACETAMOL IN HUMAN
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ABSTRACT
Comparison of the effects of a single oral dose of cimetidine and propantheline on the pharmacokinetics of paracetamol were studied with paracetamol (1g) administered alone, concurrently with cimetidine (400mg), delay (1 hour) with cimetidine (400mg), concurrently with paracetamol (15mg) and delay (1 hour) with propantheline (15mg) respectively. Paraetamol concentration was measured in saliva of 8 healthy male, non-smokers and non-alcoholic volunteers. A log data and AUC curves were used to generate pharmacokinetic data and the data obtained compared pharmacokinetically and statistically. On concurrent administration of paracetamol and cimetidine, the pharmacokinetic parameters change where as follows – Cmax decrease by 16%, T1/2ab increase by 2%, Kab increase by 9.0%, T1/2el decrease by 1.9%, Kel decrease by 10%, lag time increase by 11% while the AUC decreases by 19%. On concurrent administration of paracetamol and propantheline the following were observed – decrease in Cmax by 11%, incease in T1/2ab by 1.6%, Kab decrease by 9%, T1/2el increase by 25%, Kel decrease by 17%, lag time increase by 66% while the AUC decrease by 70%. On delayed administration i.e. paracetamol (1g) admistered an hour after the administration of 15mg propantheline there was decrease in Cmax by 45% (P>0.05), increase in T1/2 by 67%, decrease in Kab 31% (P>0.05), IX increase in lag time by 11% (P0.01), increase clearance (P0.05). Qualitative and quantitative differences can be said to exist between the effect of cimetidine and propantheline on the absorption kinetics of paracetamol as seen in the percentage changes of the pharmacokinetic parameters. Even with inter-individual variability accounting for some significance changes, it can be concluded that cimetidine, unlike propantheline does not alter the absorption kinetics of paracetamol on concurrent administration but delayed administration, hence no serious therapeutic implications of the combination of the two drugs in therapy. There was pronounced alteration of the absorption kinetics of paracetamol Propanthaline but are not of any clinical significance.
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