Population pharmacokinetic model of rifampicin for personalized tuberculosis pharmacotherapy: Effects of SLCO1B1 polymorphisms on drug exposure.

English summary

This multicenter prospective cohort study developed a population pharmacokinetic model of rifampicin in Korean patients with tuberculosis, incorporating body weight and SLCO1B1 rs4149056 genotype, and proposed initial doses for different weight bands.

Key points

• A total of 879 patients with tuberculosis were analyzed using a training dataset of 510 patients and a test dataset of 359 patients.
• A one-compartment model incorporating allometric scaling for body size best described rifampicin pharmacokinetics.
• Apparent clearance (CL/F) was 16.6% higher in the SLCO1B1 rs4149056 wild-type group than in the variant group, resulting in significantly lower rifampicin exposure in the wild-type group. The developed model was reported to have better predictive performance than previously published models. The study proposed initial rifampicin doses of 450, 600, 750, and 1050 mg/day for patients weighing <40 kg, 40–55 kg, 55–70 kg, and >70 kg, respectively.

Audience

Clinicians, researchers, and advanced students interested in rifampicin pharmacokinetics, therapeutic drug monitoring in tuberculosis, pharmacogenomics, and precision dosing

Scope and limitations

The findings are based on a multicenter prospective cohort from Korea and on nonlinear mixed-effects modeling and simulations. The proposed doses are model-based initial doses; the supplied text does not establish that they improve treatment outcomes or reduce drug resistance. Because the study population was limited to Korean patients with tuberculosis, generalizability to other populations is uncertain.

Research context

A neutral thematic connection to Sangzin Ahn’s portfolio is the use of pharmacokinetic variability, population modeling, and pharmacogenomics to support precision dosing for tuberculosis treatment.