Abstract
Purpose: 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-acetyltransferase-2 (NAT2) status on the PK properties of INH.
Methods: 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 C(max)( )and AUC estimates for all INH dosages.
Findings: Ninety studies were included in this systematic review. TB status significantly affected the INH C max and AUC estimates. In healthy volunteers, the dose-normalized INH C-max and AUC were statistically higher than those of patients with TB. No significant differences were found in dose-normalized C-max 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 dosenormalized C-max and AUC of pediatric patients with TB and TB/HIV with their respective adult counterparts. Dose-normalized INH C-max and AUC in patients with fast and intermediate NAT2 were significantly lower than in patients with slow NAT2. (C) 2020 Elsevier Inc.