title: Effect of ranitidine on the pharmacokinetics of triazolam and alpha-hydroxytriazolam in both young (19-60 years) and older (61-78 years) people.
abstract: 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.
authors.affiliation: GlaxoWellcome, Research Triangle Park, NC, USA. ROC27451@glaxowellcome.com
authors.forename: R L
authors.initials: RL
authors.lastname: O'Connor-Semmes
authors.forename: K
authors.initials: K
authors.lastname: Kersey
authors.forename: D H
authors.initials: DH
authors.lastname: Williams
authors.forename: R
authors.initials: R
authors.lastname: Lam
authors.forename: K M
authors.initials: KM
authors.lastname: Koch
mesh_terms: 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*
chemical_list: D014151:Anti-Anxiety Agents; D000897:Anti-Ulcer Agents; D014229:Triazolam; C028638:alpha-hydroxytriazolam; D011899:Ranitidine