title: Effects of type 2 diabetes mellitus on the population pharmacokinetics of rifampin in tuberculosis patients.
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.
authors.affiliation: 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.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Chang
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Chae
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Hwi-Yeol
authors.initials: HY
authors.lastname: Yun
authors.affiliation: 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.
authors.forename: Jangik I
authors.initials: JI
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsangbuk-do, Republic of Korea.
authors.forename: Hye Duck
authors.initials: HD
authors.lastname: Choi
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jihye
authors.initials: J
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Jong Sun
authors.initials: JS
authors.lastname: Park
authors.affiliation: 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.
authors.forename: Young-Jae
authors.initials: YJ
authors.lastname: Cho
authors.affiliation: 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.
authors.forename: Ho Il
authors.initials: HI
authors.lastname: Yoon
authors.affiliation: 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.
authors.forename: Choon-Taek
authors.initials: CT
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Wan Gyoon
authors.initials: WG
authors.lastname: Shin
authors.affiliation: 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.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000904:Antibiotics, Antitubercular / Q000097:blood / Q000493:pharmacokinetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008956:Models, Chemical; D011446:Prospective Studies; D012293:Rifampin / Q000097:blood / Q000493:pharmacokinetics*; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000904:Antibiotics, Antitubercular; D012293:Rifampin
keywords: Antituberculosis agents; NONMEM; Population pharmacokinetics; Rifampin; Tuberculosis