Oncology PBPKADC

Enfortumab vedotin and MMAE disposition

Reference paper ↗

A reduced ADC–payload disposition model linking enfortumab vedotin concentration to formation and elimination of the released MMAE payload and their cumulative exposures.

Therapeutic
Enfortumab vedotin
Modality
Antibody–drug conjugate (ADC)
Target
PVRL4, Nectin-4
Disease
Nectin-4-positive cancers and MMAE drug–drug interaction assessment
Model type
PBPK, ADC

Complete model workspace

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Parameters
4
States
5
Equations
5
Derived outputs
5

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EV 1.25 mg/kg single dose reduced

How does enfortumab vedotin disposition drive MMAE formation, concentration, and cumulative exposure? Explore this intervention regimen through Enfortumab vedotin concentration, MMAE concentration, Cumulative ADC exposure, Cumulative MMAE exposure.

Starting result

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Starting configuration

Time: 0–7 day; step 0.05

InputDefaultAvailable range
ADC decay0.7733 1/day0.3866–1.16 1/day
MMAE formation0.1186 (ng/mL/day)/(ug/mL)0.0593–0.1779 (ng/mL/day)/(ug/mL)
MMAE elimination0.2273 1/day0.1136–0.3409 1/day

Expected readouts

ADC concentration (ug/mL) · MMAE concentration (ng/mL) · Cumulative ADC exposure (ug*day/mL) · Cumulative MMAE exposure (ng*day/mL)

Adjustable model parameters

This public explorer exposes 3 curated parameters. Sign in to edit all 4 declared model parameters.

How the model represents the biology

A reduced ADC–payload disposition model linking enfortumab vedotin concentration to formation and elimination of the released MMAE payload and their cumulative exposures.

How do enfortumab vedotin exposure, MMAE formation, and elimination evolve?Enfortumab vedotin input establishes ADC exposure. ADC undergoes loss and separately drives formation of released MMAE, which undergoes its own elimination. Both concentrations accumulate separate exposure integrals, and a rifampin scenario changes the MMAE elimination parameter.BIOLOGY OVERVIEWHow do enfortumab vedotin exposure, MMAE formation, and elimination evolve?Enfortumab vedotinModeled ADC inputADC exposureCentral ADC concentrationADC lossFirst-order concentration lossReleased MMAESeparate payload concentrationMMAE eliminationScenario-sensitive loss rateADC + MMAE exposureTwo separate concentrationintegralsRifampin settingChanges MMAE elimination onlyPRIMARY READOUTSADC concentrationADC concentrationMMAE concentrationMMAE concentrationADC exposureADC exposureMMAE exposureMMAE exposure

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

Model scope: Nectin-4 binding, tissue PBPK compartments, intracellular cleavage, tumor killing, rifampin PK, and an explicit CYP3A pathway are not represented.

Modeled relationships (7)
  • Enfortumab vedotin → ADC exposure: ADC input (flow)
  • ADC exposure → ADC loss: ADC decay (loss)
  • ADC exposure → Released MMAE: formation drive (production)
  • Released MMAE → MMAE elimination: payload loss (loss)
  • ADC exposure → ADC + MMAE exposure: ADC AUC (production)
  • Released MMAE → ADC + MMAE exposure: MMAE AUC (production)
  • Rifampin setting → MMAE elimination: changes k (modulation)

Modeled relationships: Enfortumab vedotin to ADC exposure: ADC input (flow); ADC exposure to ADC loss: ADC decay (loss); ADC exposure to Released MMAE: formation drive (production); Released MMAE to MMAE elimination: payload loss (loss); ADC exposure to ADC + MMAE exposure: ADC AUC (production); Released MMAE to ADC + MMAE exposure: MMAE AUC (production); Rifampin setting to MMAE elimination: changes k (modulation).

Primary readouts: ADC concentration; MMAE concentration; ADC exposure; MMAE exposure.

Found a scientific issue? Email helpdesk@unibiointelligence.com with model ID choules_2024_enfortumab_vedotin_adc_pbpk_ddi.

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

Ubi Biologics