Mechanism for the interaction between triazolam and cimetidine

✍ Scribed by Steven R. Cox; Patricia D. Kroboth; Paul H. Anderson; Randall B. Smith

• Publisher: John Wiley and Sons
• Year: 1986
• Tongue: English
• Weight: 454 KB
• Volume: 7
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510070606

✦ Synopsis

Four normal volunteers each received three intraduodenal infusions of 0.5 mg triazolam solutions. Three treatments were:

1. a pH 2.3 solution in which 47 per cent of the dose had hydrolysed to form a triazolo-benzophenone (TB); 2. a pH 6.0 solution containing negligible TB; 3. the p H 6.0 solution administered during cimetidine treatment (1200 mg day-').

TB was stable in serum and only very low T B serum concentrations were observed from the p H 2.3 treatment. No difference was observed in any triazolam pharmacokinetic parameter between the p H 6.0 and the p H 2.3 treatments. Cimetidine increased the triazolam AUC, and C,,, by 54 and 35 per cent, respectively. These results indicate that T B undergoes extensive presystemic conversion to triazolam and the triazolam-cimetidine interaction occurs primarily through a reduction in triazolam clearance.