Population pharmacokinetics of levofloxacin in breastmilk in patients with rifampicin‐resistant tuberculosis
Levofloxacin is a widely used antibiotic included in rifampicin-resistant tuberculosis (RR-TB) treatment. Data describing levofloxacin concentrations in breastmilk and infant exposure are limited. We analysed data from two South African studies of breastfeeding women receiving levofloxacin (750-1000 mg daily) for RR-TB. Plasma and breastmilk samples were collected over eight hours, ≥5 weeks postpartum. A single plasma sample was obtained from breastfed infants. Twenty women contributed paired plasma-breastmilk samples, 15 plasma concentrations from breastfed infants were available. Using nonlinear mixed-effects modelling, levofloxacin equilibrated rapidly between plasma and breastmilk (7.50 min half-life; 95% CI: 3.89-11.5), with a breastmilk: plasma ratio of 1.46 (95% CI: 1.40-1.52). The relative infant dose through breastfeeding was 6-8% of the recommended 15-20 mg/kg/day adult and paediatric dose, confirmed by low (but detectable) concentrations in some infants. It is unclear whether these low infant concentrations may be prophylactic or instead contribute to the development of drug resistance.
Authors
- Richard Court (ORCID: https://orcid.org/0000-0002-7927-6506)
- Gary Maartens (ORCID: https://orcid.org/0000-0003-3080-6606)
- Lubbe Wiesner (ORCID: https://orcid.org/0000-0002-9070-8699)
- Paolo Denti (ORCID: https://orcid.org/0000-0001-7494-079X)
- Marian Loveday (ORCID: https://orcid.org/0000-0001-9205-9314)
- Francesca Conradie (ORCID: https://orcid.org/0000-0002-0194-3559)
- Catriona John Waitt (ORCID: https://orcid.org/0000-0003-0134-5855)
- Buyisile Mkhize (ORCID: https://orcid.org/0000-0003-4022-3156)
- Lufina Tsirizani
- Sharon Sawe (ORCID: https://orcid.org/0009-0003-7251-8546)
Institutions
- South African Medical Research Council (ZA)
- University of Liverpool (GB)
- University of Cape Town (ZA)
- University of the Witwatersrand (ZA)
- Centre for the AIDS Programme of Research in South Africa (ZA)
- Liverpool Women's Hospital (GB)
- Infectious Diseases Institute (UG)
- Makerere University (UG)
Publication Details
- Journal
- British Journal of Clinical Pharmacology
- Published
- 2025-12-02
- DOI
- https://doi.org/10.1002/bcp.70386
- Primary Topic
- Tuberculosis Research and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- United States Agency for International Development
- Wellcome Trust
- International Maternal Pediatric Adolescent AIDS Clinical Trials Network
- National Institute for Health and Care Research
- South African Medical Research Council
- University of Cape Town
- National Institutes of Health
- Medical Research Council
- National Institute of Mental Health
- National Institute of Allergy and Infectious Diseases
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development