Summary
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.
Article PDF
Similar content being viewed by others
References
Albin H, Vinçon G, Pehourcq F, Dangoumau J (1982) Influence de la josamycine sur la pharmacocinétique de la carbamazépine. Thérapie 37: 151–156
Amédée-Manesme O, Rey E, Brussieux J, Goutières F, Aicardi J (1982) Antibiotiques à ne jamais associer à la carbamazépine. Arch Fr Pédiatr 39: 126
Baktir G, Fich HU, Huguenin P, Bircher J (1983) Triazolam concentration-effect relationships in healthy subjects. Clin Pharmacol Ther 34: 195–201
Brazier JL, Kofman J, Faucon G, Perrin-Fayolle M, Lepape A, Lanoue R (1980) Retard d'élimination de la théophylline dû à la troléandomycine. Thérapie 35: 545–549
Carry PV, Ducluzeau R, Jourdan C, Bourrat Ch, Vigneau C, Descotes J (1982) De nouvelles interactions avec les macrolides? Lyon Med 248: 189–190
Cummins LH, Kozak PP Jr, Gilman SA (1977) Erythromycin's effect on theophylline blood level. Pediatrics 59: 144–145
Gurwich EL, Cohon MS, Olree JP, Cramer RL, Pugsley JA (1985) Pharmacokinetic profile triazolam Halcion tablets. Drug Information, Upjohn Services Unit
Hills M, Armitage P (1979) The two period cross-over clinical trial. Br J Clin Pharmacol 8: 7–20
Hindmarch I (1980) Psychomotor function and psychoactive drugs. Br J Clin Pharmacol 10: 189–209
Lister RG (1985) The amnesic action of benzodiazepines in man. Neurosci Biobehav Rev 9: 87–94
Ludden TM (1985) Pharmacokinetic interactions of the macrolide antibiotics. Clin Pharmacokinet 10: 63–79
Pfeifer HJ, Greenblatt DJ, Friedman P (1979) Effects of three antibiotics on theophylline kinetics. Clin Pharmacol Ther 26: 36–40
Scavone JM, Greenblatt DJ, Friedman H, Shader RI (1986) Enhanced bioavailability of triazolam following sublingual versus oral administration. J Clin Pharmacol 26: 208–210
Szefler SJ, Brenner M, Jusko WJ, Spector SL, Flesher KA, Ellis EF (1982) Dose and time-related effect of troleandomycin on methylprednisolone elimination. Clin Pharmacol Ther 32: 166–171
Wechsler D (1955) A manual for the Wechsler Adult Intelligence Scale. Psychological Corporation New York
Weinberger M, Hudgel D, Spector S, Chidsey C (1977) Inhibition of theophyllin clearance by troleandomycin. J Allergy Clin 59: 229–231
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Warot, D., Bergougnan, L., Lamiable, D. et al. Troleandomycin-triazolam interaction in healthy volunteers: Pharmacokinetic and psychometric evaluation. Eur J Clin Pharmacol 32, 389–393 (1987). https://doi.org/10.1007/BF00543975
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00543975