Population pharmacokinetics and dose evaluation for second-line TB drugs in patients with diabetes
Abstract
BACKGROUNDTo evaluate currently recommended dosage using the population pharmacokinetics (PK) of bedaquiline (BDQ), clofazimine, cycloserine, linezolid (LZD) and moxifloxacin (MFX) in patients with multidrug-resistant TB (MDR-TB) and type II diabetes mellitus (DM).METHODSA prospective multi-centre PK study was conducted in China between 2016 and 2019. Population PK models were developed using nonlinear mixed-effect analyses based on the blood samples collected by rich sampling. The probability of target attainment (PTA) analysis was estimated using the Monte Carlo simulation.RESULTSA total of 1,450 plasma samples were collected from 58 participants with DM. Simulations showed that the WHO-recommended regimens of LZD (600 mg daily) and MFX (400 mg daily) achieved > 90% PTA for M. tuberculosis isolates with MICs below 0.50 and 0.25 mg/L, respectively. The currently recommended BDQ regimen (400 mg daily for 2 weeks, followed by 200 mg thrice weekly) might fail to achieve >90% PTA at an MIC of 0.06 mg/L or higher.CONCLUSIONThe population PK models for the five second-line drugs were established in Chinese patients with MDR-TB and DM. The model-based dosage evaluation showed that dosing adjustments may be necessary for isolates with borderline resistance levels..
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 58 participants or records.
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