Isoniazid
Isoniazid. Bactericidal anti-TB agent — prodrug activated by mycobacterial KatG to nicotinoyl-NAD adduct, inhibits InhA enoyl-ACP reductase →… Oral half-life 3.7 h.
Bactericidal anti-TB agent — prodrug activated by mycobacterial KatG to nicotinoyl-NAD adduct, inhibits InhA enoyl-ACP reductase → blocks mycolic-acid synthesis. NAT2 acetylator polymorphism drives clearance variability (~3-fold). Hepatotoxicity + B6-deficiency peripheral neuropathy (B6 supplementation mandatory).
PK: zero-content, and V 42 L WAS AN AUC — the abstract only 42s are exposures of "42.24 +/- 8.51 mg/h/L" and "42.19 +/- 8.80", read as a volume in litres; the stored 3 h looks likewise to be its "3 h post-dose" sampling timepoint. The intravenous row hung on an oral-only study. Re-sourced to a population fit in 45 healthy participants and 157 patients (PMID:35928262): "The estimated absorption rate constant (Ka), oral clearance (CL/F), and apparent volume of distribution (V2/F) for INH were 3.94 +/- 0.44 h-1 ... and 56.8 +/- 5.53 L" — a GENUINE published absorption rate, and one that is 2.8 TIMES the template default it replaces. Because that volume is apparent, F is pinned to 1; the real absolute bioavailability is 93% fasted against 78% fed. ACETYLATION IS BIMODAL SO NO SCALAR IS TRULY VALID: half-lives are 1.54 h in rapid and 3.68 h in slow acetylators, and the mixture proportion is population-specific. The slow-acetylator arm is stored as the higher-exposure case and labelled. The intramuscular route is removed as unsupported.
Pharmacokinetics
- Oral — t½ 3.7 h · F 100% · ka 3.94 h⁻¹ · Vd 56.8 L
- IV — t½ 3.7 h · F 100% · Vd 56.8 L
Sources: PMID:21980963, PMID:35928262, PMID:8275616, PMID:26661397