Effects of type 2 diabetes mellitus on the population pharmacokinetics of rifampin in tuberculosis patients

Min Jung Chang, Jung Woo Chae, Hwi Yeol Yun, Jangik I. Lee, Hye Duck Choi, Jihye Kim, Jong Sun Park, Young Jae Cho, Ho Il Yoon, Choon Taek Lee, Wan Gyoon Shin, Jae Ho Lee

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Abstract

Summary Diabetes mellitus (DM) is a well-known risk factor to develop tuberculosis (TB). Some reports indicate the serum concentrations of anti-TB drugs are lower in patients with TB and DM than those with TB only. Therefore, we developed a nonlinear mixed-effects model (NONMEM) to determine the population PK parameters of rifampin and assessed the effects of DM status in patients with TB. One-compartment linear modeling with first-order absorption was evaluated using the 206 plasma samples of rifampin from 54 patients with DM. Based on the final model, DM affected the absorption rate constant (ka) and the volume of distribution (Vd) of rifampin. The body mass index (BMI) of the patients affected rifampin clearance (CL). The ka of rifampin in patients with TB and DM was greater than that in patients with TB only. Further, the predicted Vd in patients with DM was greater than that in patients without DM. As Vd is inversely correlated with plasma concentrations, the rifampin concentrations were predicted to be lower in the patients with DM. The authors recommend administering the greater doses of rifampin for the treatment of TB in patients with DM compared with the doses for the patients without DM to prevent treatment failure.

Original languageEnglish
Pages (from-to)54-59
Number of pages6
JournalTuberculosis
Volume95
Issue number1
DOIs
Publication statusPublished - 2015 Jan 1

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All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Chang, M. J., Chae, J. W., Yun, H. Y., Lee, J. I., Choi, H. D., Kim, J., Park, J. S., Cho, Y. J., Yoon, H. I., Lee, C. T., Shin, W. G., & Lee, J. H. (2015). Effects of type 2 diabetes mellitus on the population pharmacokinetics of rifampin in tuberculosis patients. Tuberculosis, 95(1), 54-59. https://doi.org/10.1016/j.tube.2014.10.013