Effect of study protocol on the interactions between cimetidine and paracetamol in man.

The influence of cimetidine (400 mg) on the salivary pharmacokinetics of oral paracetamol (1 g) was studied in 8 healthy subjects under two protocols--concomitant and delayed administration of cimetidine. There were no significant changes in the salivary pharmacokinetics of paracetamol when the two drugs were concomitantly administered (P > 0.100). Delayed administration of paracetamol 1 h after cimetidine, on the other hand, was associated with significant changes as compared to control. The peak salivary concentration (Cmax) and absorption rate constant (Kab) were significantly reduced (P < 0.05), while the time to peak concentration (Tmax), absorption half-life constant (t1/2ab) and lag time were all significantly increased (P < 0.05). Elimination half-life (t1/2el) was also significantly increased (P < 0.05). These findings indicated that cimetidine does not affect the pharmacokinetics of paracetamol when the two drugs were concomitantly administered but impaired the absorption of paracetamol when the administration of the latter was delayed by 1 h after cimetidine. The therapeutic implication of this interaction is that the efficacy of paracetamol may be affected.