ArticleThe Journal of antimicrobial chemotherapy2024
Sarecycline pharmacokinetics/pharmacodynamics in the hollow-fibre model of Mycobacterium avium complex: so near and yet so far.
Article in The Journal of antimicrobial chemotherapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.
- A systematic review of tetracyclines for nontuberculous mycobacteria: focus on rapidly growing mycobacteria.European respiratory review : an official journal of the European Respiratory Society · 2025Pooled it
- Novel regimens for treatment ofbioRxiv : the preprint server for biology · 2026Article
- Efficacies of Sequenced Monotherapies of Mycobacterium avium Lung Infection in Mouse.The Journal of infectious diseases · 2026Article
- Rifamycin-, macrolide-, and ethambutol-free combinations to treatThe international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2026Article
- Omadacycline for peritoneal dialysis-associated peritonitis caused byFrontiers in medicine · 2026Article
- Efficacies of sequenced monotherapies ofbioRxiv : the preprint server for biology · 2025Article
- Tigecycline pharmacodynamics in the hollow fiber system ofbioRxiv : the preprint server for biology · 2025Article
- Comparative efficacy of tetracyclines against isolates ofIJTLD open · 2025Article
- Tigecycline pharmacodynamics in the hollow fiber system ofFrontiers in pharmacology · 2025Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPoor sustained sputum culture conversion rates with the standard-of-care therapy highlight the need for better drugs to treat Mycobacterium avium complex pulmonary disease (MAC-PD).
objectiveTo determine the pharmacokinetics/pharmacodynamics (PK/PD)-optimized exposure of sarecycline and its potential role in treating MAC-PD.
methodsWe performed MIC studies with MAC ATCC 700898 and 19 clinical isolates and test-tube static concentration-response studies. A dynamic hollow-fibre system model of intracellular MAC (HFS-MAC) study was performed mimicking six human-equivalent sarecycline dose concentration-time profiles to identify the PK/PD optimal exposure of sarecycline for MAC kill. The inhibitory sigmoid maximal effect (Emax) model was used for PK/PD analysis.
resultsThe sarecycline MIC of MAC ATCC 700898 was 1 mg/L, while the MIC for the 19 clinical strains ranged between 32 and >256 mg/L. The concentration mediating 50% of Emax (EC50) was similar between intracellular and extracellular MAC. In the HFS-MAC, all six sarecycline doses killed intracellular MAC, with an Emax of 1.0 log10 cfu/mL below Day 0 burden (stasis). The sarecycline EC80 (optimal) exposure was identified as AUC0-24/MIC = 139.46.
conclusionsSarecycline demonstrated anti-MAC Emax in the HFS-MAC model better than ethambutol but worse than omadacycline (>5 log10 cfu/mL below stasis) in HFS-MAC. However, since currently approved highest oral sarecycline dose achieves an AUC0-24 of 48.2 mg·h/L and MAC MICs are >32 mg/L, the target AUC0-24/MIC of 139.46 is unlikely to be achieved in patients.
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