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Tuberculosis (Edinb). 2015 Jan;95(1):54-9. doi: 10.1016/j.tube.2014.10.013. Epub 2014 Nov 15.

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

Author information

1
Department of Pharmacy, College of Pharmacy, Yonsei University, Incheon, Republic of Korea; Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, Republic of Korea; Department of Pharmaceutical Medicine and Regulatory Science, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, Republic of Korea.
2
College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
3
College of Pharmacy, Yeungnam University, Gyeongsangbuk-do, Republic of Korea.
4
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
5
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-Si, Gyeonggi-Do, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
6
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-Si, Gyeonggi-Do, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: jhlee7@snubh.org.

Abstract

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.

KEYWORDS:

Antituberculosis agents; NONMEM; Population pharmacokinetics; Rifampin; Tuberculosis

PMID:
25482224
DOI:
10.1016/j.tube.2014.10.013
[Indexed for MEDLINE]

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