ArticleThe Journal of infectious diseases2022
Pharmacogenetics of Between-Individual Variability in Plasma Clearance of Bedaquiline and Clofazimine in South Africa.
Article in The Journal of infectious diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Effect of HIV on bedaquiline and delamanid pharmacokinetics in patients with multidrug-resistant TB.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2025Trial
- Exposure-QTc modeling of bedaquiline, pretomanid, and clofazimine in adults with tuberculosis.Antimicrobial agents and chemotherapy · 2026Article
- Article
- Characterization of the complex TB pharmacogenomic landscape in Africa using bioinformatic tools.Briefings in bioinformatics · 2025Article
- Characterization of NAT, GST, and CYP2E1 Genetic Variation in Sub-Saharan African Populations: Implications for Treatment of Tuberculosis and Other Diseases.Clinical pharmacology and therapeutics · 2025Article
- Review
- A Nanopore Sequencing-based Pharmacogenomic Panel to Personalize Tuberculosis Drug Dosing.American journal of respiratory and critical care medicine · 2024Article
- The landscape of very important pharmacogenes variants and potential clinical relevance in the Chinese Jingpo population: a comparative study with worldwide populations.Cancer chemotherapy and pharmacology · 2024Article
- Multidrug-resistant tuberculosis.Nature reviews. Disease primers · 2024Review
- Pharmacogenetics as part of recommended precision medicine for tuberculosis treatment in African populations: Could it be a reality?Clinical and translational science · 2023Review
- Human Cytochrome P450 1, 2, 3 Families as Pharmacogenes with Emphases on Their Antimalarial and Antituberculosis Drugs and Prevalent African Alleles.International journal of molecular sciences · 2023Review
- Article
- Model-Predicted Impact of ECG Monitoring Strategies During Bedaquiline Treatment.Open forum infectious diseases · 2022Article
- Clinical standards for the dosing and management of TB drugs.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2022Article
- Review
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 4 countries.
Funding
Abstract
backgroundPlasma bedaquiline clearance is reportedly more rapid with African ancestry. Our objective was to determine whether genetic polymorphisms explained between-individual variability in plasma clearance of bedaquiline, its M2 metabolite, and clofazimine in a cohort of patients treated for drug-resistant tuberculosis in South Africa.
methodsPlasma clearance was estimated with nonlinear mixed-effects modeling. Associations between pharmacogenetic polymorphisms, genome-wide polymorphisms, and variability in clearance were examined using linear regression models.
resultsOf 195 cohort participants, 140 were evaluable for genetic associations. Among 21 polymorphisms selected based on prior genome-wide significant associations with any drug, rs776746 (CYP3A5∗3) was associated with slower clearance of bedaquiline (P = .0017) but not M2 (P = .25). CYP3A5∗3 heterozygosity and homozygosity were associated with 15% and 30% slower bedaquiline clearance, respectively. The lowest P value for clofazimine clearance was with VKORC1 rs9923231 (P = .13). In genome-wide analyses, the lowest P values for clearance of bedaquiline and clofazimine were with RFX4 rs76345012 (P = 6.4 × 10-7) and CNTN5 rs75285763 (P = 2.9 × 10-8), respectively.
conclusionsAmong South Africans treated for drug-resistant tuberculosis, CYP3A5∗3 was associated with slower bedaquiline clearance. Different CYP3A5∗3 frequencies among populations may help explain the more rapid bedaquiline clearance reported in Africans. Associations with RFX4 and CNTN5 are likely by chance alone.
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Registered trials
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