ArticleClinical pharmacokinetics2026
Towards Model-Informed Precision Dosing of High-Dose Rifampicin: A Parsimonious Population Pharmacokinetic Model Capturing Saturation and Autoinduction in Tanzanian and South African Patients with Tuberculosis.
Article in Clinical pharmacokinetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
7 authors.
Funding
Abstract
backgroundRifampicin, a cornerstone of tuberculosis treatment, exhibits complex pharmacokinetics with variable absorption, saturable elimination and time-dependent autoinduction, together with marked inter- and intra-individual variability in drug exposure. These properties challenge standard weight-based dosing and underscore the need for individualized strategies, particularly in high-burden settings like Tanzania. While therapeutic drug monitoring (TDM) supported by model-informed precision dosing (MIPD) is being implemented, few of the existing population pharmacokinetic (popPK) models includes Tanzanians and are parsimonious.
objectiveThis study aimed to develop a parsimonious popPK model of rifampicin that successfully captures both its autoinductive and saturable elimination components, achieving predictive performance comparable to more complex reference models described in the literature.
methodsRifampicin concentrations data from 42 Tanzanian and 92 South African patients, covering doses up to 50 mg/kg over 2 weeks were used to develop the model, which was further benchmarked against literature reference models.
resultsThe chosen model employed a one-compartment structure with Michaelis-Menten elimination and a time-dependant E
conclusionThese findings support the implementation of MIPD and TDM to improve efficacy and safety in TB treatment rather than relying on a uniform dosing approach based on bodyweight. This model provides a robust foundation for individualized dosing and the deployment of clinical decision support tools in high TB burden settings.
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Registered trials
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