Eun Sun Kim1,2, Byoung Soo Kwon1,2, Jong Sun Park1,2, Jae-Yong Chung3,4, Soo Hyun Seo5,6, Kyoung Un Park5,6, Junghan Song, Seonghae Yoon4, Jae Ho Lee1,2. 1. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. 2. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. 3. Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine, Seoul, Republic of Korea. 4. Clinical Trials Center, Seoul National University Bundang Hospital, Seongnam, Korea. 5. Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. 6. Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Abstract
AIM: Rifampin is one of key drugs for the treatment of tuberculosis (TB). Little is known for the relationship between the rifampin pharmacokinetics and genetic polymorphisms in Asian population. We aimed to investigate relationship between genetic polymorphism of SLCO1B1 and rifampin exposure and its impact on clinical outcomes in Korean patients with active pulmonary TB. METHODS: From February 2016 to December 2019, patients with active pulmonary TB who were taking rifampin more than one week were prospectively enrolled. Serial or one-time blood sampling was conducted to determine rifampin concentrations. The genotype of 4 single nucleotide polymorphisms (SNPs) of SLCO1B1 was determined. To estimate the drug clearance and exposure, population pharmacokinetics analysis was conducted. Clinical outcomes such as time to AFB culture conversion, chest radiograph score changes from baseline, and all-cause mortality were also evaluated. The exposure among different SLCO1B1 genotype was compared and relationship between drug exposure and clinical outcomes were explored. RESULTS: A total of 105 patients (70 males and 35 females) were included in the final analysis. The mean age of patients was 55.4 years. The mean drug clearance and exposure were 13.6 L/h and 57.9 mg⋅h/L, respectively. The genetic polymorphisms of SLCO1B1 were not related to rifampin clearance or exposure. As the rifampin exposure increased, the chest radiographs improved significantly. But the duration of AFB culture conversion was not related to the drug exposure. CONCLUSIONS: SLCO1B1 gene polymorphisms did not influence rifampin concentrations and clinical outcomes in Korean patients with active pulmonary TB. This article is protected by copyright. All rights reserved.
AIM: Rifampin is one of key drugs for the treatment of tuberculosis (TB). Little is known for the relationship between the rifampin pharmacokinetics and genetic polymorphisms in Asian population. We aimed to investigate relationship between genetic polymorphism of SLCO1B1 and rifampin exposure and its impact on clinical outcomes in Korean patients with active pulmonary TB. METHODS: From February 2016 to December 2019, patients with active pulmonary TB who were taking rifampin more than one week were prospectively enrolled. Serial or one-time blood sampling was conducted to determine rifampin concentrations. The genotype of 4 single nucleotide polymorphisms (SNPs) of SLCO1B1 was determined. To estimate the drug clearance and exposure, population pharmacokinetics analysis was conducted. Clinical outcomes such as time to AFB culture conversion, chest radiograph score changes from baseline, and all-cause mortality were also evaluated. The exposure among different SLCO1B1 genotype was compared and relationship between drug exposure and clinical outcomes were explored. RESULTS: A total of 105 patients (70 males and 35 females) were included in the final analysis. The mean age of patients was 55.4 years. The mean drug clearance and exposure were 13.6 L/h and 57.9 mg⋅h/L, respectively. The genetic polymorphisms of SLCO1B1 were not related to rifampin clearance or exposure. As the rifampin exposure increased, the chest radiographs improved significantly. But the duration of AFB culture conversion was not related to the drug exposure. CONCLUSIONS:SLCO1B1 gene polymorphisms did not influence rifampin concentrations and clinical outcomes in Korean patients with active pulmonary TB. This article is protected by copyright. All rights reserved.