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 150 mg) on the pharmacokinetics of triazolam (0.25 mg) and its major metabolite, alpha-hydroxytriazolam, in both young and older people. Metabolite data were used to distinguish the mechanism of this interaction.


METHODS
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 the 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 area under the concentration-time curve from time zero to infinity [AUC(0-infinity)] was 10% and 28% higher after treatment with 75 mg and 150 mg ranitidine, respectively. In the older group, mean triazolam AUC(0-infinity) was 31% and 28% higher after treatment with 75 mg and 150 mg ranitidine, respectively. There was no change in the alpha-hydroxytriazolam/triazolam AUC(0-infinity) ratio in either age group, indicating that neither formation nor elimination of alpha-hydroxytriazolam was affected by ranitidine. There were no changes in the half-life of triazolam or alpha-hydroxytriazolam.


CONCLUSIONS
Ranitidine increases oral absorption of triazolam in both young and older people. This effect is likely caused by elevation of gastrointestinal pH, allowing for greater absorption of acid-labile triazolam. The difference in this effect between age groups at the lower 75-mg dose of ranitidine suggests that older people may be more sensitive to the antisecretory effect of ranitidine.
O'Connor-Semmes
R L
RL
GlaxoWellcome, Research Triangle Park, NC, USA. ROC27451@glaxowellcome.com
Kersey
K
K
Williams
D H
DH
Lam
R
R
Koch
K M
KM
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood / Q000378:metabolism*; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D011899:Ranitidine / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014229:Triazolam / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*
D014151:Anti-Anxiety Agents; D000897:Anti-Ulcer Agents; D014229:Triazolam; C028638:alpha-hydroxytriazolam; D011899:Ranitidine