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Model-based precision dosing and remedial dosing recommendations for delayed or missed doses of isoniazid in Chinese patients with tuberculosis
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  • Jinmeng Li,
  • Ruoyang Zhang,
  • Gaoyi Yang,
  • Qingshan Cai,
  • Yazhen Lang,
  • Fangming Zhong,
  • Jinpeng Huang,
  • Yuanyuan Chen,
  • Yao Qin,
  • Likui Fang,
  • Bo Ye,
  • Lihua Lin,
  • Huihong Lin,
  • Xinjun Cai,
  • Kan Xu
Jinmeng Li
Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine
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Ruoyang Zhang
Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine
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Gaoyi Yang
Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine
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Qingshan Cai
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Yazhen Lang
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Fangming Zhong
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Jinpeng Huang
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Yuanyuan Chen
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Likui Fang
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Huihong Lin
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Xinjun Cai
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Kan Xu
Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine

Corresponding Author:[email protected]

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Abstract

Aim: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large inter-individual variability was found in its pharmacokinetics, and how to handle a delayed or missed dose of INH remains unclear. This study aimed to develop a population pharmacokinetics (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for non-adherent patients. Methods: A nonlinear mixed-effects modeling was used to analyze the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens. A two-compartment model well described the PPK of INH. Results: N-acetyltransferase 2 (NAT2) genotype and body weight were identified as significant factors on INH PK. Monte Carlo simulations determined optimal dosage regimens for patients with different NAT2 genotype and body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. On delaying a INH dose exceed 12 h, only need to take the next single dose normally. Conclusion: PPK modeling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.
04 Sep 2023Submitted to British Journal of Clinical Pharmacology
11 Sep 2023Submission Checks Completed
11 Sep 2023Assigned to Editor
11 Sep 2023Review(s) Completed, Editorial Evaluation Pending
14 Sep 2023Reviewer(s) Assigned
24 Oct 2023Editorial Decision: Revise Major