학술논문
The effect of anti-tuberculosis drug pharmacokinetics on QTc prolongation.
Document Type
Academic Journal
Author
Jin Y; Department of Biostatistics and Bioinformatics, Emory Rollins School of Public Health, Atlanta, Georgia.; Benkeser D; Department of Biostatistics and Bioinformatics, Emory Rollins School of Public Health, Atlanta, Georgia.; Kipiani M; National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia.; Maranchick NF; Department of Pharmacy, University of Florida, Gainesville, Florida.; Mikiashvili L; National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia.; Barbakadze K; National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia.; Avaliani Z; National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia.; Alghamdi WA; Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.; Alshaer MH; Department of Pharmacy, University of Florida, Gainesville, Florida.; Peloquin CA; Department of Pharmacy, University of Florida, Gainesville, Florida.; Blumberg HM; Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia.; Kempker RR; Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia. Electronic address: rkempke@emory.edu.
Source
Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 9111860 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7913 (Electronic) Linking ISSN: 09248579 NLM ISO Abbreviation: Int J Antimicrob Agents Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Implementation of newer anti-tuberculosis (TB) drugs may prolong the QT interval, increasing the risk of arrythmias and sudden cardiac death. The potential for cardiac adverse events has prompted recommendations for frequent cardiac monitoring during treatment. However, unknowns remain, including the association between drug concentrations and QT interval.
Methods: An observational prospective cohort study design was used. Patients undergoing treatment for drug-resistant TB in Georgia were assessed. Serial blood samples were collected at 4-6 weeks for pharmacokinetics. Electrocardiograms were recommended to be performed monthly. A generalized estimating equation spline model was used to investigate (1) the effect difference between bedaquiline and delamanid, (2) the cumulative effect of number of anti-TB drugs, and (3) the relationship between serum drug concentrations on QTc interval.
Results: Among 94 patients receiving either bedaquiline (n = 64) or delamanid (n = 30)-based treatment, most were male (82%), and the mean age was 39 years. The mean maximum QTc increase during the first six months was 37.5 ms (IQR: 17.8-56.8). Bedaquiline- and delamanid-based regimens displayed similar increased mean QTc change from baseline during drug administration (P = 0.12). Increasing number of anti-TB drugs was associated with an increased QTc (P = 0.01), but participants trended back towards baseline after drug discontinuation (P = 0.25). A significant association between AUC, Cmin , C max , and increased QTc interval was found for bedaquiline (months 1-6) and levofloxacin (months 1-12).
Conclusion: Bedaquiline- and delamanid-based regimens and increasing number of QT prolonging agents led to modest increases in the QTc interval with minimal clinical effect.
(Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)
Methods: An observational prospective cohort study design was used. Patients undergoing treatment for drug-resistant TB in Georgia were assessed. Serial blood samples were collected at 4-6 weeks for pharmacokinetics. Electrocardiograms were recommended to be performed monthly. A generalized estimating equation spline model was used to investigate (1) the effect difference between bedaquiline and delamanid, (2) the cumulative effect of number of anti-TB drugs, and (3) the relationship between serum drug concentrations on QTc interval.
Results: Among 94 patients receiving either bedaquiline (n = 64) or delamanid (n = 30)-based treatment, most were male (82%), and the mean age was 39 years. The mean maximum QTc increase during the first six months was 37.5 ms (IQR: 17.8-56.8). Bedaquiline- and delamanid-based regimens displayed similar increased mean QTc change from baseline during drug administration (P = 0.12). Increasing number of anti-TB drugs was associated with an increased QTc (P = 0.01), but participants trended back towards baseline after drug discontinuation (P = 0.25). A significant association between AUC, C
Conclusion: Bedaquiline- and delamanid-based regimens and increasing number of QT prolonging agents led to modest increases in the QTc interval with minimal clinical effect.
(Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)