ArticleAntimicrobial agents and chemotherapy2025
The effect of pregnancy on the population pharmacokinetics of levofloxacin in South Africans with rifampicin-resistant tuberculosis.
Article in Antimicrobial agents and chemotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Optimizing Levofloxacin Dosing for Multidrug-resistant Tuberculosis in Low-Fat-Free Mass Asian Populations.American journal of respiratory and critical care medicine · 2025Article
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11 authors.
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Abstract
Levofloxacin is a key drug in the prevention and treatment of rifampicin-resistant tuberculosis (RR-TB). There are limited data describing the effect of pregnancy on the pharmacokinetics of levofloxacin. We aimed to characterize the pharmacokinetics of levofloxacin in adults with RR-TB, including the effect of pregnancy. We pooled data from two studies conducted in adult participants treated for RR-TB in South Africa. Treatment regimens in both studies included levofloxacin dosed at 750/1000 mg daily, depending on body weight. We analyzed data from 47 participants, 31 (66%) living with HIV, using nonlinear mixed-effects modeling in NONMEM v7.5.1. Out of 33 female participants, 21 were pregnant, of whom 12 contributed matched antepartum and postpartum pharmacokinetic profiles. Levofloxacin followed one-compartment pharmacokinetics with first-order elimination and absorption with transit absorption compartments. The clearance and volume of distribution for a typical non-pregnant participant (weight: 58 kg; age: 32 years; serum creatinine: 56.2 µmol/L) were 6.06 (95% confidence interval [CI], 5.47 to 6.53) L/h and 85.9 (95% CI, 80.6 to 91.7) L, respectively. Higher serum creatinine levels were associated with lower levofloxacin clearance using a power function with an exponent of -0.367 (95% CI, -0.493 to -0.104). Pregnancy increased levofloxacin clearance by 38.1% (95% CI, 23.4% to 57.1%), with substantially lower exposures in pregnant compared with non-pregnant participants receiving equivalent weight-based doses. To achieve non-pregnant equivalent exposures of levofloxacin, an additional 250 mg tablet may be required, although further study is needed to assess the safety implications of a higher recommended dose in pregnant women.
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