Assessment of the effect of a single oral dose of telithromycin on sotalol‐induced qt interval prolongation in healthy women

Abstract

AimsTelithromycin belongs to ketolides, a new class of macrolide antibiotics. Macrolides are known to have the potential to prolong QT interval duration. Previous studies have shown that telithromycin did not induce significant QT interval prolongation in healthy subjects compared with placebo. The main objective of this study was to demonstrate the absence of amplification of QT interval prolongation induced by sotalol, when telithromycin and sotalol were co-administered. The secondary objective was to correlate the QT interval changes induced by the study drugs to plasma concentrations during the elimination phase. MethodsTwenty-four women received sotalol (160 mg) together with placebo or telithromycin (800 mg) in a two-period, double-blind, randomized study. Electrocardiograms were recorded at rest. Comparison of maximal corrected QT interval (QTc max ) with sotalol in the presence or absence of telithromycin was performed. The relation between sotalol concentration and QTc was studied using linear regression. ResultsMean difference (95% CI) between QTc max with sotalol-placebo and QTc max with sotalol-telithromycin was -15.5 ms ( -27.7 to -3.2 ms). QTc max interval prolongation was lower ( P < 0.05) with sotalol-telithromycin than with sotalol-placebo, in relation to decreased sotalol plasma concentrations. Regression analysis showed that the relationship between sotalol plasma concentration and QTc interval duration was not modified by telithromycin co-administration. ConclusionOur results do not support a potential synergistic effect on QT interval prolongation between sotalol and telithromycin. The decrease of mean QTc interval in subjects taking telithromycin and sotalol may be explained by a decrease of sotalol concentration.

Involvement of influx and efflux transport systems in gastrointestinal absorption of celiprolol

“…3), and citrus juice inhibited oral absorption of at least acebutolol, atenolol and celiprolol in human 11–15. It was also reported that gastrointestinal absorption of sotalol was inhibited by coadministration of elithromycin 17. Thus, substantial transport by OATP‐A of β‐blockers (Fig.…”

“…Oral absorption of atenolol and celiprolol was also reduced by orange juice 13, 15. Coadministration of therapeutic agents including verapamil and telithromycin has also been reported to reduce oral bioavailability of talinolol and sotalol, respectively 16, 17. One of feasible hypotheses may be that a certain constituents in the juice inhibits uptake process of these β‐blockers from apical side in the small intestinal epithelial cells, although such drug–food interactions may also be explained by other possibilities including inhibitory effect on gastric emptying rate and/or lowering effect on intestinal pH, leading to decrease in unionized form of β‐blockers.…”

Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

“…The authors suggest the increased oral bioavailability and reduced renal clearance to be caused by P-gp inhibition [ 185 ]. When sotalol was co-administered with telithromycin the sotalol C max decreased by 34% and AUC by 27%, leading to a decreased QTc interval by 15.5 ms [ 186 ]. Co-administration of ERY with talinolol resulted in a significant increase in talinolol AUC and C max [ 187 ], and co-administration with felodipine resulted in an increase of felodipine AUC and C max [ 188 ].…”

Cytochrom-P450 mediierte Arzneimittelinteraktionen mit Antibiotika

“…Telithromycin ist ein Opfer des Rifampicins. Ähnliche Wirkeinbußen von Telithromycin werden durch die gleichzeitige Gabe der CYP3A4 Induktoren Phenytoin, Carbamazepin und Phenobarbital, aber auch für Johanniskraut Präparate beschrieben[26][27][28].…”