Cardiovascular Drugs: Statin Dose-Response Lab

Statin Therapy

Statin Atorvastatin

Daily dose 20 mg

Simulated speed 2.0 d/s

Hepatic metabolism (CYP3A4) 1.00×

Day

0.0

Plasma conc.

0 ng/mL

Reductase inhibition

LDL-C

190 mg/dL

How it works

Every dose is absorbed from the gut into plasma, metabolised by the liver, and — once there — competitively blocks HMG-CoA reductase, the enzyme hepatocytes use to build cholesterol. Less enzyme activity means less LDL synthesised, so circulating LDL-C drifts down over days toward a new, lower steady state.

PK (one-compartment, oral):
 dA/dt = −ka·A          (gut)
 dC/dt = ka·A/Vd − ke·C (plasma)

PD (Hill equation, enzyme block):
 Inhibition = Imax·Cⁿ / (IC50ⁿ + Cⁿ)

LDL kinetics:
 dLDL/dt = ksyn·(1−Inhibition) − kclear·LDL

Statin — sets absorption rate ka, elimination half-life and IC50 (binding potency); rosuvastatin is slow-cleared and potent, simvastatin is fast-cleared and weaker.
Daily dose — amount reaching the gut compartment each 24h; higher doses push plasma concentration further past IC50 on the Hill curve, but returns diminish once inhibition nears its Imax ceiling.
Simulated speed — LDL turnover takes days-to-weeks in real patients; this compresses that into seconds so you can watch the new steady state emerge.
Hepatic metabolism — models CYP3A4 activity variability between patients (drug interactions, genetics): faster clearance (>1×) needs a higher dose for the same effect, slower clearance raises plasma levels and risk of side effects at a given dose.

Real-world relevance: this is the actual mechanism behind statin therapy for hyperlipidaemia — the single most prescribed cardiovascular drug class — and the same Hill-equation / compartment-model pattern underlies how any enzyme-inhibiting drug's dose translates into a measurable physiological outcome.

LDL-C over time

LDL particle Liver / HMG-CoA reductase Arterial deposit site

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