Triazolam Azithromycin

Figure 3 Rates of formation of 4-OH-triazolam from triazolam (250 pM) by human liver microsomes in vitro. Each point is the mean ( SE) of four microsomal preparations. Reaction velocities when preparations were preincubated with the macrolide agents are expressed as a percentage of the control velocity with no inhibitor present (inhibitor = 0). Mean IC50 were TAO, 3.3 pM erythromycin, 27.3 pM clarithromycin, 25.2 pM azithromycin, >250 pM. Abbreviations IC50, 50% inhibitory concentrations TAO, troleandomycin. Source Adapted, in part, from Ref. 77.

Figure 5 Mean plasma TRZ concentrations following a single 0.125-mg oral dose of TRZ administered in Trials B, C, D, and E, as described in the text and in Fig. 4. Abbreviations TRZ, triazolam CLAR, clarithromycin ERY, erythromycin AZ, azithromycin PL, placebo. Source From Ref. 77.

Triazolam plasma concentrations were determined by gas chromatography with electron capture detection (73,95). The pharmacokinetic results demonstrated that mean clearance during Trials B and C were nearly identical (413 and 416 mL/min, respectively) that is, coadministration of azithromycin had no effect on the pharmacokinetics of triazolam (Fig. 5). However, triazolam clearance was significantly reduced to 146 mL/min by erythromycin (Trial D) and to 95 mL/min by clarithromycin (Trial E). Thus, the in vivo kinetic results are highly consistent with the in vitro data. 

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... 

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). 

In a randomized, double-blind, pharmacokinetic-pharmacodynamic study, 12 volunteers took placebo or triazolam 0.125 mg orally, together with placebo, azithromycin, erythromycin, or clarithromycin. The apparent oral... 

The serum levels and effects of midazolam, triazolam and zopi-clone are markedly increased and prolonged by erythromycin. The same interaction has been seen with clarithromycin, josamy-cin, or troleandomycin but not azithromycin. Alprazolam would be expected to be similarly affected. Other benzodiazepines, and the related hypnotic zaleplon, appear not to interact with the macrolides to a clinically significant extent... 

Azithromycin. A clinical study in 12 healthy subjects found that azithromycin did not affect the pharmacokinetics of a single 125-microgram dose of triazolam. These results were supported by an in vitro study, which confirmed that azithromycin was only a weak inhibitor of triazolam metabolism. ... 

Azithromycin does not interact with midazolam or triazolam, and the effects of roxithromycin on midazolam and triazolam, and of erythromycin on diazepam, flunitrazepam, nitrazepam, temazepam and zopiclone or clarithromycin on zolpidem appear to be small and unimportant, or the effects negligible, so that no special precautions seem to be necessary. 

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