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Pyrazinamide (PZA)

Antitubercularprescriptionoral · inferred

First-line tuberculosis drug in the standard RIPE regimen (Rifampin+Isoniazid+Pyrazinamide+Ethambutol). Prodrug activated by mycobacterial pyrazinamidase (pncA) only in acidic environments (pH ~5.5), giving it unique sterilizing activity against semi-dormant bacilli inside macrophage phagolysosomes. This acid-dependent activation is what allows the 6-month short-course regimen — PZA kills the persister population that rifampin and isoniazid cannot reach. Hepatotoxicity is dose-related and additive with other RIPE drugs. Hyperuricemia from inhibited urate excretion — can precipitate gout.

Projected serum levels — 1.5k mg, once daily

Pyrazinamide (PZA)
Pyrazinamide (PZA) modeled serum levels, 1.5k mg once daily over 15 days Population-based pharmacokinetic estimate. Steady state reached after approximately 1 days. 0 500 1k 1.5k 2k Day 0 Day 4 Day 8 Day 11 Day 15 Time on a regular schedule ≈ steady state · day 1
Pyrazinamide (PZA) modeled serum levels with a loading dose of 1.8k mg, then 1.5k mg once daily The first dose is larger so levels approach steady state faster. 0 500 1k 1.5k 2k Day 0 Day 4 Day 8 Day 11 Day 15 Time on a regular schedule

Maintenance schedule: 1.5k mg once daily (oral).

Loading schedule: 1.8k mg on day 1, then 1.5k mg once daily — reaching therapeutic levels sooner.

Modeled steady state after ~1 days: peak ≈ 1.5k mg, trough ≈ 316 mg body load. Population-based estimate over 15 days for a 1.5k mg dose at a 70 kg reference body mass — the interactive app scales curves to your doses, timing, and body mass.

Key facts

Category
Antitubercular
Route modeled
Oral
Model confidence
inferred
Half-life
9.5 h
Common dose
1.5k mg
Suggested maximum
2k mg/day
Reference dose range
1k–2k mg (single dose)
Suggested cadence
once daily
Validated against
1.5k mg oral — Cmax 45 mg/L at 2 h

Documented interactions

  • moderate
    Allopurinol + Pyrazinamide (PZA) CYP inhibition

    Allopurinol mechanism_based of xanthine_oxidase predicted to change Pyrazinamide (PZA) AUC by ~1.82x

Serum checks 1 modeled interaction pairings for pyrazinamide (pza) across your whole stack — absorption conflicts, enzyme inhibition, and nutrient depletion included.

Research behind this entry

  1. The curious characteristics of pyrazinamide: a review Zhang Y, Mitchison D · International Journal of Tuberculosis and Lung Disease, 2003

    Seminal review explaining PZA's unique acid-dependent sterilizing activity against semi-dormant Mycobacterium tuberculosis in macrophage phagolysosomes, establishing the mechanistic basis for why PZA enables 6-month…

  2. Pyrazinamide and pyrazinoic acid activity against tubercle bacilli in cultured human macrophages and in mice Salfinger M et al. · Journal of Antimicrobial Chemotherapy, 1990 DOI

    Demonstrated that pyrazinamide requires phagolysosomal acidification for activity against intracellular M. tuberculosis, with pyrazinoic acid accumulation in acidic compartments reaching 10-20x extracellular…

2 published studies referenced in the app, each with a plain-language summary.