Pham Quang Hoa (인제대학교 의과대학) | 한빛사논문 > 한빛사

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Pham Quang HoaPham Quang Hoa

인제대학교 의과대학

Int. J. Antimicrob. Agents, Nov 15 2023, S0924-8579(23)00323-0 | https://doi.org/10.1016/j.ijantimicag.2023.107034 Population Pharmacokinetic Model of Rifampicin for Personalized Tuberculosis Pharmacotherapy: Effects of SLCO1B1 Polymorphisms on Drug Exposure

Pham Quang Hoa ^1,2, Kim Hyun Kuk ⁴, Tae Won Jang ⁵, Hyewon Seo⁶, Jee Youn Oh ⁷, Ho Cheol Kim ⁸, Ah Young Shin ⁹, Jinsoo Min ¹⁰, Rannissa Puspita Jayanti ^1,2, Tran Minh Hung ^1,2, Nguyen Ky Anh ^1,2, Sangzin Ahn ^1,2, Nguyen Phuoc Long ^1,2, Yong-Soon Cho ^1,2, Jae-Gook Shin ^1,2,3 on behalf of thecPMTb

¹Center for Personalized Precision Medicine of Tuberculosis, Inje University College of Medicine, Busan, Republic of Korea

²Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea

³Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Republic of Korea

⁴Division of Pulmonology, Department of Internal Medicine, Inje University Haeundae Paik Hospital

⁵Pulmonary Division, Dept of Internal Medicine, Kosin University Gospel Hospital

⁶Division of Pulmonary Medicine, Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea

⁷Division of Pulmonology, Department of Internal Medicine, Korea University Guro Hospital

⁸Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Korea

⁹Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

¹⁰Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

Co-corresponding Author: Yong-Soon Cho, MD, PhD

Corresponding Author and Principal Investigator: Jae-Gook Shin, MD, PhD

Abstract

Rifampicin 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. This multicenter prospective cohort study in Korea analyzed demographic and clinical data, the solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotypes, and rifampicin concentrations. Population PK modelling and simulations were conducted using nonlinear mixed-effect modelling. 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 rifampicin doses of 450, 600, 750, and 1050 mg/day, respectively. 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.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-11-23)
연구진국내 연구진
분야 의약학 > 약리의학

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