Earticle

초록

영어

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 Ct 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 predicted 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.

목차

ABSTRACT
Methods
1. Clinical study in patients with tuberculosis
2. Exploration: Relationship between single point Cp and AUC
3. Complementary analysis: Physiologically based pharmacokineticmodeling and simulation
Results
1. Clinical study in patients with tuberculosis
2. Exploration: Relationship between single point Cp and AUC
3. Complementary analysis: Physiologically based pharmacokineticmodeling and simulation
Discussion
Conclusion
Acknowledgment
Conflict of Interest
References

키워드

저자

• Minseo Kang [ College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea ]
• Hayun Lim [ College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea ]
• Eun Sun Kim [ Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea ]
• Jong Sun Park [ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea ]
• Jae Ho Lee [ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea ]
• Eunjin Hong [ College of Pharmacy, Dongguk University, Goyang 10326, Republic of Korea ] Corresponding Author
• Jangik I. Lee [ College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea ] Corresponding Author

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  한국임상약학회지 [Korean Journal of Clinical Pharmacy]

• 간기

  계간

• pISSN

  1226-6051

• 수록기간

  1991~2026

• 등재여부

  KCI 등재

• 십진분류

  KDC 518 DDC 615