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

Title
Effects of type 2 diabetes mellitus on the population pharmacokinetics of rifampin in tuberculosis patients
Author(s)
장민정[장민정]채정우[채정우]윤휘열[윤휘열]이장익[이장익]최혜덕김지혜[김지혜]박종선[박종선]조영재[조영재]윤호일[윤호일]이준택[이준택]신완균[신완균]이재호[이재호]
Keywords
ACTIVE PULMONARY TUBERCULOSIS; ANTITUBERCULOSIS DRUGS; OBESITY; IMPACT; OUTCOMES
Issue Date
201501
Publisher
CHURCHILL LIVINGSTONE
Citation
TUBERCULOSIS, v.95, no.1, pp.54 - 59
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. (C) 2014 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/33680http://dx.doi.org/10.1016/j.tube.2014.10.013
ISSN
1472-9792
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약학대학 > 약학부 > Articles
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