Evaluation of the Effects of a Monthly Buprenorphine Depot Subcutaneous Injection on QT Interval During Treatment for Opioid Use Disorder

Clinical Pharmacology and Therapeutics
Virginia D SchmithMalcolm A Young

Abstract

Extensive 12-lead electrocardiogram monitoring and drug concentrations were obtained during development of BUP-XR, a monthly subcutaneous injection for the treatment of opioid use disorder (OUD). Matched QT and plasma drug concentrations (11,925) from 1,114 subjects were pooled from 5 studies in OUD. A concentration-QT model was developed, which accounted for confounding factors (e.g., comedications) affecting heart rate and heart rate-corrected QT interval (QTc). Bias-corrected nonparametric two-sided 90% confidence intervals (CIs) were derived for the mean predicted effect of BUP-XR on QTc (ΔQTc) at therapeutic and supratherapeutic doses. Changes in QTc were associated with age, central vs. noncentral reading, sex, methadone, and barbiturates. The upper 90% CI of ΔQTc was 0.29, 0.67, and 1.34 ms at the steady-state peak concentration (Cmax ) for 100, 300, and 2 × 300 mg doses, respectively. An effect of BUP-XR on QT can be ruled out at therapeutic and supratherapeutic doses of BUP-XR, after accounting for covariates that may influence heart rate and QT interval in OUD.

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Citations

Dec 1, 2018·Future Oncology·Randy EricksonWilliam Nibley
Jan 27, 2019·Current HIV/AIDS Reports·Laura FanucchiP Todd Korthuis
May 10, 2019·Journal of Comparative Effectiveness Research·Lee S SchwartzbergJonathan Kish
Aug 11, 2019·Der Nervenarzt·Michael Soyka, Oliver Pogarell
Jan 16, 2021·Journal of the American College of Cardiology·Mori J KrantzMark C P Haigney
Aug 13, 2020·Infectious Disease Clinics of North America·David P SerotaMarcos C Schechter
Apr 9, 2021·Peptides·Richard J Bodnar

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Software Mentioned

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NONMEM
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