Triazolam pharmacodynamic effects

For most child psychiatrists, the drug interactions most frequently encountered are interactions with other psychotropics. Fluoxetine inhibits the CYP3A isozymes and thus increase the plasma concentration of the tria-zolobenzodiazepines (alprazolam, midazolam, and triazolam), causing increased psychomotor effects (Shader and Greenblatt, 1995). To avoid unwanted psychomotor effects, the dosage of alprazolam should be decreased when it is coadministered with fluoxetine (Chouinard et ah, 1999). Nefazadone has also been shown to increase the pharmacodynamic effects of triazolam and, to a lesser extent, alprazolam (Chouinard et ah, 1999). 

Isradipine. Isradipine 5 mg daily reduced the AUC of a single 250-microgiam dose of triazolam by 20% in 9 healthy subjects, but no difference in the pharmacodynamic effects of triazolam were seen. ... 

The pharmacodynamic data indicated that the benzodiazepine agonist effects of triazolam plus placebo (Trial B) and of triazolam plus azithromycin (Trial C) were similar to each other and greater than the effects of placebo plus placebo (Trial A). However, coadministration of erythromycin (Trial D) or... 

Fahey JM, Pritchard GA, von Moltke LL, et al. The effects of ketoconazole on triazolam pharmacokinetics, pharmacodynamics and benzodiazepine receptor binding in mice. J Pharmacol Exp Ther 1998 285 271-276. 

Greenhlatt DJ, Harmatz JS, von Moltke LL, et al. Age and gender effects on the pharmacokinetics and pharmacodynamics of triazolam, a cytochrome P450 3A substrate. Clin Pharmacol Ther 2004 76 467 479. 

In a randomized, double-bhnd, pharmacokinetic-pharmacodynamic study, 12 volunteers took placebo or triazolam 0.125 mg orally, together with placebo, azithromycin, erythromycin, or clarithromycin. The apparent oral clearance of triazolam was significantly reduced by erythromycin and clarithromycin. The peak plasma concentration was correspondingly increased, and the half-life was prolonged. The effects of triazolam on dynamic measures were nearly identical when triazolam was given with placebo or azithromycin, but benzodiazepine agonist effects were enhanced by erythromycin and clarithromycin (23). 

Diltiazem. A study in 7 healthy subjects found that diltiazem 60 mg three times daily for 3 days increased the AUC of a single 250-microgram dose of triazolam 2.3-fold and almost doubled its peak serum levels. Pharmacodynamic tests showed an increase in the sedative effects of triazolam. Another study in 10 healthy subjects found that diltiazem 60 mg three times daily for 2 days increased the AUC of a single 250-microgram dose of triazolam 3.4-fold, and approximately doubled its maximum plasma level and half-life. The pharmacodynamic changes were briefly described as profound and prolonged." In contrast, diltiazem 40 mg was found to have little or no effect on the hypnotic effects of triazolam in 16 healthy insomniacs in another study. ... 

Triazolam 500 micrograms orally was given to 10 healthy subjects before and after rifampicin 600 mg daily or a placebo for 5 days. Rifampicin reduced the triazolam AUC by 95% and decreased the maximum plasma triazolam levels by 88% when compared with the placebo group. The elimination half-life was reduced from 2.8 to 1.3 hours. Pharmacodynamic tests (drowsiness, sway, Maddox wing, etc.) showed that rifampicin abolished the effects of triazolam. ... 

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