Prediction of Rifampin Exposure using a Single Concentration-time Point in Patients with Tuberculosis
10.24304/kjcp.2025.35.3.198
- Author:
Minseo KANG
1
;
Hayun LIM
;
Eun Sun KIM
;
Jong Sun PARK
;
Jae Ho LEE
;
Eunjin HONG
;
Jangik I. LEE
Author Information
1. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea
- Publication Type:Original Article
- From:Korean Journal of Clinical Pharmacy
2025;35(3):198-207
- CountryRepublic of Korea
- Language:English
-
Abstract:
Background:Rifampin exhibits highly variable exposure in tuberculosis patients, leading to adverse effects or treatment failure.This study aimed to develop therapeutic drug monitoring (TDM) strategy for rifampin using a single concentration-time point to estimate the area under the concentration-time curve (AUC), with the potential to reduce the number of blood draws.
Methods:Plasma concentration(Cp)-time data were obtained from tuberculosis patients by collecting serial venous blood samples after rifampin administration. The Cp timepoint (Ct ) that predicts AUC best was explored using linear regression (Exploration). The accuracy and precision were evaluated using Bland-Altman plot. Physiologically based pharmacokinetic modeling approach was used to evaluate whether the single C t point identified in Exploration provides the best prediction of the AUC (Complement).
Results:Cp-time data obtained from 26 participants were evaluable for the determination of AUC by Ct . In Exploration, C4 best predicted the AUC (r2 =0.91, p<0.0001), followed by C2 (r2 =0.84, p<0.0001). In AUC prediction by C4 , the datapoints for predict-ed and observed AUC pairs were randomly scattered in Bland-Altman plot with the mean bias of −0.029 μg · h/mL, and the 95% limit of agreement of −21.1 to 21.1 μg · h/mL. In Complement, C4,sim best predicted the AUC (r2 =0.86, p<0.0001), which supports that C4 reliably predicted AUC.
Conclusions:For improving treatment outcomes in the treatment of tuberculosis, a single concentration monitoring is applicable to rifampin TDM instead of AUC, potentially making the process less invasive, painful and cumbersome for patients, clinicians and healthcare providers.
