OncologyCardiovascular & coagulation PopPKTMDD

Bevacizumab PK and VEGF165 target binding

Reference paper ↗

A population QSS-TMDD model coupling bevacizumab disposition to VEGF165 turnover, free antibody, target-bound complex, and total circulating VEGF165.

Therapeutic
Bevacizumab
Modality
Monoclonal antibody
Target
VEGFA, VEGF165, vascular endothelial growth factor A
Disease
Metastatic colorectal cancer
Model type
PopPK, TMDD

Complete model workspace

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Parameters
13
States
5
Equations
5
Derived outputs
27

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5 mg/kg every 2 weeks 70 kg deterministic simulation

How do bevacizumab exposure and VEGF165 turnover determine free drug, target, and complex concentrations? Explore this intervention regimen through Total bevacizumab, Free bevacizumab, Bevacizumab–VEGF165 complex, Total VEGF165, Cumulative total exposure.

Starting result

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Starting configuration

Time: 0–126 day; step 1

InputDefaultAvailable range
Systemic clearance0.18 L/day0.09–0.27 L/day
Central distribution volume3.23 L1.615–4.845 L
Intercompartmental clearance1.38 L/day0.69–2.07 L/day
Quasi-steady-state binding constant267 nM133.5–400.5 nM
Turnover loss rate0.401 1/day0.2005–0.6015 1/day

Expected readouts

Total bevacizumab · Free bevacizumab · Bevacizumab VEGF165 complex · Total VEGF165 · Cumulative total exposure (mg*day/L)

Adjustable model parameters

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More key parameters (1)

How the model represents the biology

A population QSS-TMDD model coupling bevacizumab disposition to VEGF165 turnover, free antibody, target-bound complex, and total circulating VEGF165.

How do bevacizumab disposition, VEGF165 turnover, and QSS binding interact?Intravenous bevacizumab enters a central total-drug pool, exchanges as free drug with a peripheral pool, and is removed through free-drug and complex clearance. VEGF165 is synthesized and turned over, while an algebraic quasi-steady-state allocation determines free drug, free target, and drug-target complex.BIOLOGY OVERVIEWHow do bevacizumab disposition, VEGF165 turnover, and QSS binding interact?IV bevacizumabDose to central total drugCentral bevacizumabTotal state with algebraicfree drugPeripheral free drugReversible distributionVEGF165 synthesisBaseline production andturnoverTotal VEGF165Dynamic circulating targetpoolQSS drug–targetcomplexAlgebraic binding allocationSystemic removalFree drug, target and complexlossPRIMARY READOUTSTotal bevacizumabTotal bevacizumabFree bevacizumabFree bevacizumabDrug–VEGF complexDrug–VEGF complexTotal VEGF165Total VEGF165Cumulative exposureCumulative exposure

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

Model scope: Explicit association or dissociation kinetics, a dynamic complex state, tissue VEGF compartments, angiogenesis, tumor response, and clinical efficacy are not represented; binding is algebraic QSS.

Modeled relationships (8)
  • IV bevacizumab → Central bevacizumab: IV input (flow)
  • Central bevacizumab ↔ Peripheral free drug: free-drug exchange (reversible exchange)
  • VEGF165 synthesis → Total VEGF165: target synthesis (production)
  • Central bevacizumab → QSS drug–target complex: QSS allocation (modulation)
  • Total VEGF165 → QSS drug–target complex: QSS allocation (modulation)
  • Central bevacizumab → Systemic removal: free-drug CL (loss)
  • QSS drug–target complex → Systemic removal: complex CL (loss)
  • Total VEGF165 → Systemic removal: target turnover (loss)

Modeled relationships: IV bevacizumab to Central bevacizumab: IV input (flow); Central bevacizumab reversibly exchanges with Peripheral free drug: free-drug exchange (reversible exchange); VEGF165 synthesis to Total VEGF165: target synthesis (production); Central bevacizumab to QSS drug–target complex: QSS allocation (modulation); Total VEGF165 to QSS drug–target complex: QSS allocation (modulation); Central bevacizumab to Systemic removal: free-drug CL (loss); QSS drug–target complex to Systemic removal: complex CL (loss); Total VEGF165 to Systemic removal: target turnover (loss).

Primary readouts: Total bevacizumab; Free bevacizumab; Drug–VEGF complex; Total VEGF165; Cumulative exposure.

Found a scientific issue? Email helpdesk@unibiointelligence.com with model ID panoilia_2015_bevacizumab_vegf165_qss_tmdd.

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

Ubi Biologics