Journal article
A Systematic Review and Meta-analysis of Isoniazid Pharmacokinetics in Healthy Volunteers and Patients with Tuberculosis
Clinical therapeutics, Vol.42(11), pp.e220-e241
11/2020
DOI: 10.1016/j.clinthera.2020.09.009
PMID: 33032843
Abstract
This systematic review and meta-analysis assesses the pharmacokinetic (PK) summary estimates of isoniazid (INH) between healthy volunteers and patients with tuberculosis (TB), evaluates whether the current INH dose regimen is appropriate in patients with TB, and evaluates the impact of N-acetyl-transferase-2 (NAT2) status on the PK properties of INH.
A systematic approach was conducted to find studies with relevant INH PK data published in the English language up to February 2018. The PK properties of INH were extracted with their respective INH dosages and were dose normalized to allow a fair comparison between healthy volunteers and patients with TB. Meta-analysis was then performed for the Cmax and AUC estimates for all INH dosages.
Ninety studies were included in this systematic review. TB status significantly affected the INH Cmax and AUC estimates. In healthy volunteers, the dose-normalized INH Cmax and AUC were statistically higher than those of patients with TB. No significant differences were found in dose-normalized Cmax and AUC between adults with TB and adults with TB/HIV; however, the AUC in pediatric patients was significantly different between patients with TB and patients with TB/HIV. In addition, no significance was observed comparing the dose-normalized Cmax and AUC of pediatric patients with TB and TB/HIV with their respective adult counterparts. Dose-normalized INH Cmax and AUC in patients with fast and intermediate NAT2 were significantly lower than in patients with slow NAT2.
The current recommended dosages of INH were found to produce less drug exposure in patients with TB when compared with healthy volunteers. NAT2 polymorphism greatly impacts the PK properties of INH; hence, testing for acetylator status is highly recommended, and therapeutic drug monitoring would help reduce INH toxicity.
•TB status significantly affects INH Cmax and AUC leading to lower drug exposure•Current INH dosing regimen for TB adult and pediatric patients may be inadequate•INH Cmax and AUC increases as dose increases•NAT2 polymorphism impact INH concentration and may require individualized dosing
Details
- Title: Subtitle
- A Systematic Review and Meta-analysis of Isoniazid Pharmacokinetics in Healthy Volunteers and Patients with Tuberculosis
- Creators
- Boi-Lam Hong - University of IowaRonilda D'Cunha - University of IowaPeizhi Li - University of IowaMohammad H. Al-Shaer - University of FloridaWael A. Alghamdi - King Khalid UniversityGuohua An - University of IowaCharles Peloquin - University of Florida
- Resource Type
- Journal article
- Publication Details
- Clinical therapeutics, Vol.42(11), pp.e220-e241
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.clinthera.2020.09.009
- PMID
- 33032843
- ISSN
- 0149-2918
- eISSN
- 1879-114X
- Grant note
- DOI: 10.13039/100000865, name: Bill and Melinda Gates Foundation, award: OPP1031105
- Language
- English
- Date published
- 11/2020
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984366034602771
Metrics
15 Record Views