NAT2 Acetylator Phenotype Simulator

NAT2 Genotype

Rapid acetylator — two functional NAT2*4-type alleles. Fast enzymatic N-acetylation clears isoniazid quickly; standard once-daily dosing rarely accumulates.

Dosing

Isoniazid dose 300 mg

Simulation speed 6 h/s

Live Readouts

Plasma conc.

0.0 mg/L

Elapsed time

0.0 h

Half-life t½

1.1 h

Doses given

Steady-state accumulation ratio (24 h dosing)

1.03×

How it works

NAT2 (N-acetyltransferase 2) acetylates isoniazid in the liver. Its gene carries common SNPs (NAT2*5, *6, *7 among others) that each cut enzyme activity; the phenotype depends on how many of your two alleles are "slow":

0 slow alleles → Rapid acetylator   → t½ ≈ 1.1 h
1 slow allele  → Intermediate       → t½ ≈ 1.9 h
2 slow alleles → Slow acetylator    → t½ ≈ 3.2 h

Isoniazid follows one-compartment first-order kinetics. Each dose adds Dose/V_d to the plasma concentration; between doses it decays exponentially:

C(t) = C₀ · e^(−k·t),   k = ln(2) / t½
Repeated dosing (interval τ) accumulates to steady state:
  Accumulation ratio R = 1 / (1 − e^(−k·τ))

The particles orbiting the bloodstream loop represent circulating drug molecules; the liver lattice on the right converts them (they fade and vanish) at a rate set by k. A slow acetylator's lattice glows dimmer and clears molecules far more slowly, which is exactly why slow acetylators accumulate isoniazid over daily dosing and carry higher risk of peripheral neuropathy, while rapid acetylators clear it fast enough that standard doses can under-treat.

Active isoniazid Liver / NAT2 enzyme

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