Troleandomycin-triazolam interaction in healthy volunteers: pharmacokinetic and psychometric evaluation.
Seven healthy volunteers received a single oral dose of triazolam 0.25 mg after 7 days on troleandomycin 2 g/day p.o. or placebo in a double-blind cross-over study. Plasma triazolam and psychometric and memory tests (including Critical Flicker Fusion threshold, Choice Reaction Time, Digit Symbol Substitution and Self-Rating Scales) were assessed at regular intervals after the final treatment. Troleandomycin was found to prolong the psychomotor impairment and amnesia produced by triazolam. There was a significant enhancement of the AUC, the peak concentration and the delay to tmax of triazolam after 7 days treatment with troleandomycin compared to placebo. Thus, there is a pharmacokinetic interaction, and the combination of triazolam and troleandomycin should be avoided or the dose of triazolam should be adjusted. The most likely mechanism is a diminished hepatic first-pass effect, and a decrease in the apparent oral clearance of triazolam.
D000328:Adult; D004347:Drug Interactions; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects*; D014229:Triazolam / Q000378:metabolism / Q000494:pharmacology*; D014217:Troleandomycin / Q000494:pharmacology*
D014229:Triazolam; D014217:Troleandomycin