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

被引：36

作者：

Chang, Min Jung ^{[1
,2
,3
]}

Chae, Jung-woo ^{[4
]}

Yun, Hwi-yeol ^{[4
]}

Lee, Jangik I. ^{[1
,2
,3
]}

Choi, Hye Duck ^{[5
]}

Kim, Jihye ^{[6
,7
]}

Park, Jong Sun ^{[8
,9
]}

Cho, Young-Jae ^{[8
,9
]}

Yoon, Ho Il ^{[8
,9
]}

Lee, Choon-Taek ^{[8
,9
]}

Shin, Wan Gyoon ^{[6
,7
]}

Lee, Jae-Ho ^{[8
,9
]}

机构：

[1] Yonsei Univ, Coll Pharm, Dept Pharm, Inchon, South Korea

[2] Yonsei Univ, Coll Pharm, Yonsei Inst Pharmaceut Sci, Inchon, South Korea

[3] Yonsei Univ, Coll Med & Pharm, Dept Pharmaceut Med & Regulatory Sci, Inchon, South Korea

[4] Chungnam Natl Univ, Coll Pharm, Taejon, South Korea

[5] Yeungnam Univ, Coll Pharm, Gyeongsangbuk Do, South Korea

[6] Seoul Natl Univ, Coll Pharm, Seoul, South Korea

[7] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul, South Korea

[8] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Div Pulm & Crit Care Med, Songnam 463707, Gyeonggi Do, South Korea

[9] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea

来源：

TUBERCULOSIS | 2015年 / 95卷 / 01期

关键词：

Tuberculosis; Rifampin; Population pharmacokinetics; Antituberculosis agents; NONMEM; ACTIVE PULMONARY TUBERCULOSIS; ANTITUBERCULOSIS DRUGS; OBESITY; IMPACT;

D O I：

10.1016/j.tube.2014.10.013

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：54 / 59

页数：6

共 30 条

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