Neurology & neurodegeneration TMDD

Erenumab PK, target binding, and receptor pharmacology

Reference paper ↗

A subcutaneous quasi-steady-state TMDD model coupling erenumab disposition to CGRP-receptor abundance, unbound antibody, drug-target complex, and cumulative exposure.

Therapeutic
Erenumab
Modality
Monoclonal antibody
Target
CGRP receptor, CALCRL, RAMP1, calcitonin gene-related peptide receptor
Disease
Migraine prevention and CGRP-receptor pharmacology
Model type
TMDD

Complete model workspace

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Parameters
17
States
6
Equations
6
Derived outputs
26

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7 mg SC every 4 weeks 75 kg deterministic simulation

How do erenumab dose and target turnover shape total drug, unbound drug, and receptor-bound complex over time? Explore this intervention regimen through Total erenumab concentration, Unbound erenumab concentration, Erenumab–receptor complex, Total CGRP receptor, Cumulative total exposure.

Starting result

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Starting configuration

Time: 0–84 day; step 1

InputDefaultAvailable range
Reference systemic clearance0.214 L/day0.107–0.321 L/day
Central distribution volume reference4.27 L2.135–6.405 L
Absorption rate constant0.432 1/day0.216–0.648 1/day
Quasi-steady-state binding constant18.8 ng/mL9.4–28.2 ng/mL
Target internalization rate0.0345 1/day0.01725–0.05175 1/day

Expected readouts

Total erenumab concentration · Unbound erenumab concentration · Erenumab receptor complex · Total cgrp receptor (ng/mL) · Cumulative total exposure

Adjustable model parameters

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More key parameters (1)

How the model represents the biology

A subcutaneous quasi-steady-state TMDD model coupling erenumab disposition to CGRP-receptor abundance, unbound antibody, drug-target complex, and cumulative exposure.

How do erenumab disposition, receptor turnover, and QSS binding determine total-drug and total-receptor exposure?Intravenous erenumab enters the central total-drug pool directly, while subcutaneous erenumab passes through a depot. Central total drug exchanges with a peripheral pool and is allocated algebraically into free drug and drug–receptor complex under a quasi-steady-state approximation. Receptor synthesis replenishes total receptor, while drug and complex removal lower the system.BIOLOGY OVERVIEWHow do erenumab disposition, receptor turnover, and QSS binding determinetotal-drug and total-receptor exposure?IV or SC erenumabCentral input or depotabsorptionSubcutaneous depotFirst-order absorptionCentral ↔ peripheraldrugTotal-drug dispositionReceptor synthesisBaseline target productionTotal receptorDynamic target poolQSS drug–receptorcomplexAlgebraic binding allocationDrug and complexremovalLinear and internalizationlossPRIMARY READOUTSTotal and free erenumabTotal and free erenumabTotal receptorTotal receptorDrug–receptor complexDrug–receptor complexCumulative exposureCumulative exposure

Solid arrows show modeled movement or change; two-headed arrows show reversible exchange; dashed arrows show modulation without material transfer.

Model scope: CIDBF efficacy, Emax, IC50, Imax, Hill response, migraine events, and a dynamic receptor-occupancy output are not represented. Binding is an algebraic QSS allocation rather than a kinetic complex state.

Modeled relationships (8)
  • IV or SC erenumab → Subcutaneous depot: SC input (flow)
  • IV or SC erenumab → Central ↔ peripheral drug: IV input (flow)
  • Subcutaneous depot → Central ↔ peripheral drug: absorption (flow)
  • Central ↔ peripheral drug → QSS drug–receptor complex: QSS allocation (modulation)
  • Receptor synthesis → Total receptor: target synthesis (production)
  • Total receptor → QSS drug–receptor complex: QSS allocation (modulation)
  • Central ↔ peripheral drug → Drug and complex removal: linear clearance (loss)
  • QSS drug–receptor complex → Drug and complex removal: complex internalization (loss)

Modeled relationships: IV or SC erenumab to Subcutaneous depot: SC input (flow); IV or SC erenumab to Central ↔ peripheral drug: IV input (flow); Subcutaneous depot to Central ↔ peripheral drug: absorption (flow); Central ↔ peripheral drug to QSS drug–receptor complex: QSS allocation (modulation); Receptor synthesis to Total receptor: target synthesis (production); Total receptor to QSS drug–receptor complex: QSS allocation (modulation); Central ↔ peripheral drug to Drug and complex removal: linear clearance (loss); QSS drug–receptor complex to Drug and complex removal: complex internalization (loss).

Primary readouts: Total and free erenumab; Total receptor; Drug–receptor complex; Cumulative exposure.

Found a scientific issue? Email helpdesk@unibiointelligence.com with model ID vu_2017_erenumab_cidbf_pkpd_tmdd.

Research use only — not for patient-specific prediction or dosing advice.

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