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Erenumab QSS PK and capsaicin response

Two-compartment QSS target-mediated antibody disposition with a direct unbound-concentration capsaicin-challenge response for fixed research histories.

Pharmacokinetic-Pharmacodynamic Relationship of Erenumab (AMG 334) and Capsaicin-Induced Dermal Blood Flow in Healthy and Migraine Subjects ↗

Pharmaceutical Research

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MODEL IN MOTION 18 sec

How do low and high SC doses change drug amount and total target?

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7 mg SC Q4W 75 kg deterministic simulation

Fixed typical-coefficient research history with specified SC or IV input; no population or clinical inference.

0–84 day

Scenario details

7 mg SC Q4W 75 kg deterministic simulation

Fixed typical-coefficient research history with specified SC or IV input; no population or clinical inference.

Readouts

Unbound concentration · ng/mL
Deterministic quantity in the declared physical source coordinate.
Total concentration · ng/mL
Deterministic quantity in the declared physical source coordinate.
Cidbf inhibition pct · percent
Deterministic quantity in the declared physical source coordinate.
Cidbf delta dbf pu · PU
Deterministic quantity in the declared physical source coordinate.
Accounted administered drug · mg
Deterministic quantity in the declared physical source coordinate.

Study purpose

  • How do the model's key biological readouts change under 7 mg sc q4w 75 kg deterministic simulation?

Assumptions

  • Fixed source point coefficients and declared SC or IV histories; no original individual fit, population draw or clinical dose advice.
  • The direct CIDBF quantity is the capsaicin-induced blood-flow increment, not resting or total skin perfusion and not a migraine outcome.
  • Target capacity and complex use the latent source drug-equivalent ng/mL coordinate, not measured receptor protein mass.
  • The nominal depot contains the full SC dose and F is applied once in absorption. Drug accounting includes presystemic nonavailability.
  • The one-hour IV input and complete calendars are declared conditional histories; original infusion duration and source figure traces are not reproduced.
  • Day coordinates and AUC in ug*day/mL remain physical under alternate time displays.

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Simulation time
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day
84 → 168

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Biology

Two-compartment QSS target-mediated antibody disposition with a direct unbound-concentration capsaicin-challenge response for fixed research histories.

Two-compartment QSS target-mediated antibody disposition with a direct unbound-concentration capsaicin-challenge response for fixed research histories.

Model details

21 parameters · 10 states · 10 equations · 58 derived outputs

Classification & API access
Therapeutic
Erenumab
Modality
Monoclonal antibody
Target
CGRP receptor
Disease / scope
Migraine prevention and CGRP-receptor pharmacology
ParameterDefaultUnitDescription
Reference systemic clearanceCL_ref_L_day0.214L/dayFixed source coefficient or declared numerical zero convention.
F bioavailabilityF_bioavailability0.74—Fixed source coefficient or declared numerical zero convention.
Half-maximal inhibitory concentrationIC50_ng_mL255ng/mLFixed source coefficient or declared numerical zero convention.
Maximum cidbf inhibitionImax_fraction0.893fractionFixed source coefficient or declared numerical zero convention.
Quasi-steady-state binding constantKss_ng_mL18.8ng/mLFixed source coefficient or declared numerical zero convention.
Intercompartmental clearanceQ_L_day3.34L/dayFixed source coefficient or declared numerical zero convention.
Central distribution volume referenceVc_ref_L4.27LFixed source coefficient or declared numerical zero convention.
Peripheral distribution volumeVp_L2.73LFixed source coefficient or declared numerical zero convention.
Baseline capsaicin induced dermal blood flowbaseline_dbf_PU398PUFixed source coefficient or declared numerical zero convention.
Body weightbody_weight_kg75kgFixed baseline context.
Cidbf hill coefficienthill_coefficient3.08—Fixed source coefficient or declared numerical zero convention.
Absorption rate constantka_1_day0.4321/dayFixed source coefficient or declared numerical zero convention.
Degradation ratekdeg_1_day0.221/dayFixed source coefficient or declared numerical zero convention.
Target internalization ratekint_1_day0.03451/dayFixed source coefficient or declared numerical zero convention.
Target synthesis rateksyn_ng_mL_day51.9ng/mL/dayFixed source coefficient or declared numerical zero convention.
Reference weightreference_weight_kg70kgFixed source coefficient or declared numerical zero convention.
Typical clearance weighttheta_cl_weight0.75—Fixed source coefficient or declared numerical zero convention.
Typical central distribution volume weighttheta_vc_weight1—Fixed source coefficient or declared numerical zero convention.
Zero amountzero_amount_mg0mgFixed source coefficient or declared numerical zero convention.
Zero concentrationzero_concentration_ng_ml0ng/mLFixed source coefficient or declared numerical zero convention.
Zero concentration squaredzero_concentration_squared0(ng/mL)²Fixed source coefficient or declared numerical zero convention.

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