Development of population pharmacokinetics model and Bayesian estimation of rifampicin exposure in Indonesian patients with tuberculosis

Soedarsono Soedarsono, Rannissa Puspita Jayanti, Ni Made Mertaniasih, Tutik Kusmiati, Ariani Permatasari, Dwi Wahyu Indrawanto, Anita Nur Charisma, Elvina Elizabeth Lius, Rika Yuliwulandari, Pham Quang Hoa, Nguyen Ky Phat, Vo Thuy Anh Thu, Nguyen Ky Anh, Sangzin Ahn, Nguyen Phuoc Long, Yong Soon Cho, Jae Gook Shin

Research output: Contribution to journalArticlepeer-review


Background: Interindividual variability in the pharmacokinetics (PK) of anti-tuberculosis (TB) drugs is the leading cause of treatment failure. Herein, we evaluated the influence of demographic, clinical, and genetic factors that cause variability in RIF PK parameters in Indonesian TB patients. Methods: In total, 210 Indonesian patients with TB (300 plasma samples) were enrolled in this study. Clinical data, solute carrier organic anion transporter family member-1B1 (SLCO1B1) haplotypes *1a, *1b, and *15, and RIF concentrations were analyzed. The population PK model was developed using a non-linear mixed effect method. Results: A one-compartment model with allometric scaling adequately described the PK of RIF. Age and SLCO1B1 haplotype *15 were significantly associated with variability in apparent clearance (CL/F). For patients in their 40s, each 10-year increase in age was associated with a 10% decrease in CL/F (7.85 L/h). Patients with the SLCO1B1 haplotype *15 had a 24% lower CL/F compared to those with the wild-type. Visual predictive checks and non-parametric bootstrap analysis indicated good model performance. Conclusion: Age and SLCO1B1 haplotype *15 were significant covariates of RIF CL/F. Geriatric patients with haplotype *15 had significantly greater exposure to RIF. The model could optimize TB pharmacotherapy through its application in therapeutic drug monitoring (clinical trial no. NCT05280886).

Original languageEnglish
Article number102325
Publication statusPublished - Mar 2023


  • Pharmacogenetic
  • Population pharmacokinetics
  • Rifampicin
  • Therapeutic drug monitoring
  • Tuberculosis


Dive into the research topics of 'Development of population pharmacokinetics model and Bayesian estimation of rifampicin exposure in Indonesian patients with tuberculosis'. Together they form a unique fingerprint.

Cite this