Effect of ranitidine on the pharmacokinetics of triazolam and alpha-hydroxytriazolam in both young (19-60 years) and older (61-78 years) people

Objective. This study evaluated the effect of oral ranitidine (75 mg and 15 0 mg) on the pharmacokinetics of triazolam. (0.25 mg) mid its major metabol ite, alpha -hydroxytriazolam, in both young and older people. Metabolite da ta were used to distinguish the mechanism of this interaction. Method: This was a randomized, open-label, 3-way crossover study. Eighteen young (19-60 years) and 12 older (61-78 years) men and women were randomly assigned to receive evening doses of triazolam 0.25 mg: (1) alone, (2) on t he third day of dosing ranitidine 75 mg twice daily for 4 days, and (3) on the third day of dosing ranitidine 150 mg twice daily for 4 days. Results. In the young group, mean triazolam a-rea under the concentration-t ime curve from time zero to infinity [AUC(0-infinity)] was 10% and 28% high er after treatment with 75 mg and 150 mg ranitidine, respectively. In the o lder group, mean triazolam AUC(0-infinity) was 31% and 28% higher after tre atment with 75 mg and 150 mg ranitidine, respectively. There was no change in the alpha -hydroxytriazolam/triazolam AUC(0-infinity) ratio in either ag e group, indicating that neither formation nor elimination of alpha -hydrox ytriazolam was affected by ranitidine. There were no changes in the half-li fe of triazolam or alpha -hydroxytriazolam. Conclusion. Ranitidine increases oral absorption of triazolam in both young and older people. This effect is likely caused by elevation of gastrointes tinal pH, allowing for greater absorption of acid-labile triazolam. The dif ference in this effect between age groups at the lower 75-mg dose of raniti dine suggests that older people may be more sensitive to the antisecretory effect of ranitidine.