Chronopharmacology: Circadian Dosing Simulator

Dosing

Dosing time (hour of day) 08:00

Dose amount 200 mg

Circadian Clearance Rhythm

Rhythm amplitude 30%

Peak-clearance hour 15:00

Live Readouts

Peak concentration C_max–

Time in therapeutic window–

Time above toxic threshold–

Therapeutic window (5–18 mg/L)

Toxic range (>18 mg/L)

Sub-therapeutic (<5 mg/L)

Dose administration marker

How it works

A one-compartment pharmacokinetic model with first-order oral absorption, but with an elimination rate constant that oscillates on a 24-hour circadian rhythm — because hepatic drug-metabolizing enzymes (CYP450 family) genuinely vary in abundance and activity across the day:

dA_gut/dt = −k_a · A_gut
dC/dt     = k_a · A_gut / V − k_e(t) · C

k_e(t) = k_e0 · [ 1 + amp · cos( 2π(t − φ) / 24 ) ]

A_gut is the amount of drug still in the gut, C is plasma concentration, V is the volume of distribution, k_a is the fixed absorption-rate constant, k_e0 is the baseline elimination-rate constant, amp is how strongly clearance swings around that baseline, and φ is the hour at which enzyme activity — and therefore clearance — peaks. The system is integrated with RK4 across a fixed 48-hour grid (dt = 0.05 h); the single dose is injected into A_gut at the chosen administration hour.

Dosing time — shifts when the impulse of drug enters the gut compartment relative to the circadian clearance cycle. The exact same dose can clear the toxic threshold if given near the elimination trough, or stay safely inside the therapeutic window if given near the elimination peak.
Dose amount — the mass of drug administered.
Rhythm amplitude — how strongly clearance swings around its baseline over 24 h; 0% collapses the model to ordinary constant-clearance PK.
Peak-clearance hour — the time of day the liver metabolizes the drug fastest (chronotype of the enzyme system).

The spiral in the scene is a polar plot of the 48-hour concentration curve: angle = hour of day, radius = which of the two simulated days, height = plasma concentration. It is exactly the reasoning behind real chronotherapy protocols — timing chemotherapy, corticosteroids or antihypertensives to the body's own metabolic clock instead of the calendar clock.

t = 0.0 h

C = 0.00 mg/L

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