Cimetidine is a H2-receptor antagonist used in the management of peptic ulcer and other acid hypersecretory conditions. It was previously thought to have no effect on gastric motility. However, other reports have shown that a change in the study protocol may affect the absorption of co-administered drugs via an effect thought to occur by a decreased rate of gastric emptying. The present study therefore seeks to evaluate the effect of Cimetidine on Paracetamol pharmacokinetics when it is administered one hour prior to Paracetamol administration and compare this to the effect produced when Hyoscine bromide; which is known to delay gastric emptying is administered prior to Paracetamol. Sixteen healthy volunteers participated in the study which was conducted in two phases. In the first phase, 1g of Paracetamol was administered orally to the volunteers and in the second phase, the volunteers were divided into two groups of eight subjects each and the first group was given 400mg of Cimetidine orally 1 hour prior to Paracetamol administration while the second group received 10mg of Hyoscine bromide orally prior to Paracetamol administration. Plasma concentration of Paracetamol was determined using a validated spectrophotometric method. Pharmacokinetic parameters were calculated using standard non-compartmental model equations. The study found that delayed administration of Paracetamol after administration of Cimetidine led to statistically significant changes (p<0.05) in some of the pharmacokinetic parameters especially the absorption parameters such as Ka, t1/2α, Cmax and Tmax as compared to the control group receiving Paracetamol alone. These effects mirror the effects produced when the anticholinergic agent Hyoscine bromide was administered prior to Paracetamol admnistration. However, the elimination parameters of Paracetamol were not significantly altered by Cimetidine.
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