Pyrazinamide
Pyrazinamide. Anti-TB prodrug activated by mycobacterial pyrazinamidase to pyrazinoic acid → disrupts membrane energetics in acidic phagosomes.… Oral half-life 9.6 h.
Anti-TB prodrug activated by mycobacterial pyrazinamidase to pyrazinoic acid → disrupts membrane energetics in acidic phagosomes. Sterilizing component allowing the standard TB regimen to shorten from 9 to 6 months. Hepatotoxicity + hyperuricemia (gout flares).
PK: half-life corrected 10 -> 9.6 h, the value its own citation actually prints — Lacroix 1989 (PMID:2737233), 9 healthy subjects, single oral 27 mg/kg, verbatim "an elimination phase of t1/2 beta = 9.6 h". ka, V and F dropped 2026-09-06: that abstract states none of them, and the stored 50 L was ~1.7x the real figure. Not adopted, and why: Wilkins 2006 (PMID:16685561) gives V/F 29.2 L but in 227 South African TB patients, and reports absorption as BIMODAL — "Absorption rate was threefold greater in fast absorbers (3.56 h(-1)) in comparison to slow absorbers (1.25 h(-1))" — which a single ka cannot represent. No human absolute bioavailability exists for pyrazinamide in any abstract; the one modern absolute-F trial dosed the other three TB drugs intravenously and pyrazinamide orally only (PMID:26661397). CAVEATS: half-life is shorter in TB patients (6.0 h, PMID:12066959) than in healthy subjects, and longer in cirrhosis (15.07 h). Acetylator status is NOT a covariate — that applies to isoniazid.
Pharmacokinetics
- Oral — t½ 9.6 h
Sources: PMID:2737233, PMID:16685561, PMID:12066959