A liver enzyme breaks this drug down at a genotype-specific rate. Poor metabolizers carry a slow variant, normal metabolizers the typical variant, and ultra-rapid metabolizers a hyperactive variant — the same enzyme family (e.g. CYP2D6) that clears roughly a quarter of all prescribed drugs.
C(t) = Σ dose·ka /(Vd·(ka−ke)) · (e^(−ke·Δt) − e^(−ka·Δt))
ke: poor ≪ normal ≪ ultra-rapid
Fixing the dose fixes how much drug enters the blood each time — but clearance (ke) decides how fast it leaves. Give six standard doses eight hours apart and a poor metabolizer's trough never fully clears before the next dose lands, so the curve climbs dose after dose into the toxic zone. An ultra-rapid metabolizer clears almost the whole dose before the next one arrives, so the curve never climbs high enough to reach the therapeutic window at all.
Pharmacogenomic-adjusted dosing scales each patient's dose to their own clearance, calculated so the regimen's peak concentration lands at the same point inside the therapeutic window for every genotype — a lower dose for poor metabolizers, the standard dose for normal metabolizers, a higher dose for ultra-rapid metabolizers.
- Therapeutic window (green band) — the concentration range where the drug works without being dangerous.
- Toxic zone (above the band) — accumulation past this line risks adverse effects.
- Subtherapeutic (below the band) — too little drug in the blood to have the intended effect.
This is the clinical case for pre-emptive pharmacogenomic testing: knowing a patient's metabolizer status before the first prescription lets a clinician pick the right starting dose instead of discovering it by trial, toxicity, or treatment failure.