Detailed Information

Cited 0 time in webofscience Cited 0 time in scopus
Metadata Downloads

Population pharmacokinetic model of rifampicin for personalized tuberculosis pharmacotherapy: Effects of SLCO1B1 polymorphisms on drug exposure

Authors
Hoa, Pham QuangKim, Hyun KukJang, Tae WonSeo, HyewonOh, Jee YounKim, Ho CheolShin, Ah YoungMin, JinsooJayanti, Rannissa PuspitaHung, Tran MinhAnh, Nguyen KyAhn, SangzinLong, Nguyen PhuocCho, Yong-SoonShin, Jae-Gook
Issue Date
Feb-2024
Publisher
Elsevier B.V.
Keywords
Pharmacogenetics; Population pharmacokinetics; Rifampicin; Therapeutic drug monitoring; Tuberculosis
Citation
International Journal of Antimicrobial Agents, v.63, no.2
Indexed
SCIE
SCOPUS
Journal Title
International Journal of Antimicrobial Agents
Volume
63
Number
2
URI
https://scholarworks.gnu.ac.kr/handle/sw.gnu/69484
DOI
10.1016/j.ijantimicag.2023.107034
ISSN
0924-8579
1872-7913
Abstract
Background: Rifampicin (RIF) exhibits high pharmacokinetic (PK) variability among individuals; a low plasma concentration might result in unfavorable treatment outcomes and drug resistance. This study evaluated the contributions of non- and genetic factors to the interindividual variability of RIF exposure, then suggested initial doses for patients with different weight bands. Methods: This multicenter prospective cohort study in Korea analyzed demographic and clinical data, the solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotypes, and RIF concentrations. Population PK modeling and simulations were conducted using nonlinear mixed-effect modeling. Results: In total, 879 tuberculosis (TB) patients were divided into a training dataset (510 patients) and a test dataset (359 patients). A one-compartment model with allometric scaling for effect of body size best described the RIF PKs. The apparent clearance (CL/F) was 16.6% higher among patients in the SLCO1B1 rs4149056 wild-type group than among patients in variant group, significantly decreasing RIF exposure in the wild-type group. The developed model showed better predictive performance compared with previously reported models. We also suggested that patients with body weights of <40 kg, 40–55 kg, 55–70 kg, and >70 kg patients receive RIF doses of 450, 600, 750, and 1050 mg/day, respectively. Conclusions: Total body weight and SLCO1B1 rs4149056 genotypes were the most significant covariates that affected RIF CL/F variability in Korean TB patients. We suggest initial doses of RIF based on World Health Organization weight-band classifications. The model may be implemented in treatment monitoring for TB patients. © 2023
Files in This Item
There are no files associated with this item.
Appears in
Collections
College of Medicine > Department of Medicine > Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Researcher Kim, Ho Cheol photo

Kim, Ho Cheol
의과대학 (의학과)
Read more

Altmetrics

Total Views & Downloads

BROWSE