Back to Search
Start Over
Solithromycin, a novel macrolide, does not prolong cardiac repolarization: a randomized, three-way crossover study in healthy subjects.
- Source :
-
The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2017 Feb; Vol. 72 (2), pp. 515-521. Date of Electronic Publication: 2016 Oct 26. - Publication Year :
- 2017
-
Abstract
- Background: Macrolide antibiotics may cause QT prolongation.<br />Objectives: To study the QT effect of a novel macrolide, solithromycin.<br />Methods: This was a thorough QT study with a three-way crossover design performed in healthy male and female subjects to evaluate the ECG effects of a novel macrolide, solithromycin. Forty-eight subjects were randomized to receive 800 mg of intravenous (iv) solithromycin, 400 mg of oral moxifloxacin and placebo in three separate treatment periods. Continuous 12 lead ECGs were recorded at a pre-dose baseline and serially after drug administration for 24 h.<br />Results: After the 40 min infusion of 800 mg of solithromycin, the geometric mean solithromycin peak plasma concentration (C <subscript>max</subscript> ) reached 5.9 (SD: 1.30) μg/mL. Solithromycin infusion caused a heart rate increase with a peak effect of 15 bpm immediately after the end of the infusion. The change-from-baseline QTcF (ΔQTcF) was similar after dosing with solithromycin and placebo and the resulting placebo-corrected ΔQTcF (ΔΔQTcF) for solithromycin was therefore small at all timepoints with a peak effect at 4 h of only 2.8 ms (upper bound of the 90% CI: 4.9 ms). Using a linear exposure-response model, a statistically significant, slightly negative slope of -0.86 ms per ng/mL (90% CI: -1.19 to -0.53; P = 0.0001) was observed with solithromycin. The study's ability to detect small QT changes was confirmed by the moxifloxacin response. Solithromycin did not have a clinically meaningful effect on the PR or QRS interval.<br />Conclusions: The study demonstrated that solithromycin, unlike other macrolide antibiotics, does not cause QT prolongation.<br /> (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Cross-Over Studies
Electrocardiography
Female
Fluoroquinolones therapeutic use
Healthy Volunteers
Humans
Macrolides blood
Macrolides therapeutic use
Male
Moxifloxacin
Placebos administration & dosage
Triazoles blood
Triazoles therapeutic use
Arrhythmias, Cardiac chemically induced
Heart Conduction System drug effects
Macrolides adverse effects
Triazoles adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2091
- Volume :
- 72
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of antimicrobial chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 27798210
- Full Text :
- https://doi.org/10.1093/jac/dkw428