Population pharmacokinetics of pyrazinamide and isoniazid in plasma and cerebrospinal fluid from South African adults with tuberculous meningitis.

ABSTRACT: Pyrazinamide and isoniazid are first-line drugs for tuberculous meningitis (TBM), but limited information is available on their plasma pharmacokinetics, and particularly cerebrospinal fluid (CSF) penetration, in patients with TBM. Any potential effect of co-administration with high-dose rifampicin, also being evaluated in trials for TBM, is unknown. Understanding this is important for dose optimisation. We characterized pyrazinamide and isoniazid plasma and CSF pharmacokinetics among adults enrolled in a phase 2 clinical trial of intensified antibiotic therapy for HIV-associated TBM. Participants were randomized to receive either standard TBM treatment (including rifampicin 10 mg/kg) or high-dose rifampicin (35 mg/kg) plus linezolid, with or without aspirin. Plasma and lumbar CSF samples w

SUBMITTER: Calderin JM 

PROVIDER: S-EPMC12327010 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature