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Four normal volunteers each received three intraduodenal infusions of 0.5 mg triazolam solutions. Three treatments were: a pH 2.3 solution in which 47 per cent of the dose had hydrolysed to form a triazolo-benzophenone (TB); a pH 6.0 solution containing negligible TB; the pH 6.0 solution administered during cimetidine treatment (1200 mg day-1). TB was stable in serum and only very low TB serum concentrations were observed from the pH 2.3 treatment. No difference was observed in any triazolam pharmacokinetic parameter between the pH 6.0 and the pH 2.3 treatments. Cimetidine increased the triazolam AUC infinity and Cmax by 54 and 35 per cent, respectively. These results indicate that TB undergoes extensive presystemic conversion to triazolam and the triazolam-cimetidine interaction occurs primarily through a reduction in triazolam clearance.
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