The effects of once-daily dosing with ranitidine and cimetidine on theophylline pharmacokinetics

Summary

Twelve healthy non-smokers (7M and 5F) completed a balanced three-way crossover investigation designed to characterise the influence of oral Cimetidine (800 mg), ranitidine (300 mg) and placebo pretreatment for 7 days on the pharmacokinetics of a 250 mg single oral dose of theophylline. The oral clearance of theophylline after ranitidine pretreatment, 4.55±1.691/h (mearr±SD) was indistinguishable from that after placebo, 4.78±1.961/h, but Cimetidine was associated with a significant 21% reduction in theophylline clearance, 3.58±1.07 1/h (P=0.006). There was a correspondingly significant increase in the terminal half-life of theophylline following Cimetidine, 6.11±1.29 hP=0.017), compared with 5.05±1.43 h and 4.88±1.45 h for placebo and ranitidine, respectively. There was no change in maximum theophylline concentration or time to maximum but following Cimetidine the plasma theophylline levels between 4 and 12 hours were 15–50% higher than following placebo (P<0.002). These data indicate a significant interaction between 800 mg Cimetidine given once daily and theophylline which is likely to be the result of enzyme inhibition. Once-daily dosing with 300 mg ranitidine had no significant effect on theophylline pharmacokinetics.