OncologyImmunology & inflammationHematology PopPKADC

Inotuzumab ozogamicin population PK

Reference paper ↗

A two-compartment population PK model for inotuzumab ozogamicin with linear and time-dependent clearance and clinically relevant body-size and disease covariates.

Therapeutic
Inotuzumab ozogamicin
Modality
Antibody–drug conjugate (ADC)
Target
SIGLEC2, CD22, B-cell receptor CD22
Disease
B-cell acute lymphoblastic leukemia and B-cell lymphoma
Model type
PopPK, ADC

Complete model workspace

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Parameters
19
States
4
Equations
4
Derived outputs
17

Explore this model

Choose a starting point to view its result. Adjust key model inputs when you want to explore a different outcome.

Starting configuration

ALL 1.8 mg/m2/cycle fractionated regimen dynamic

ALL 1.8 mg/m2/cycle fractionated regimen dynamic

How do regimen and time-dependent clearance shape inotuzumab ozogamicin concentration and exposure? Explore this intervention regimen through Central inotuzumab ozogamicin, Cumulative ADC exposure, Total clearance, Clearance-desensitization rate.

Starting result

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Starting configuration

Time: 0–1,848 hour; step 24

InputDefaultAvailable range
Baseline linear clearance0.113 L/h0.0565–0.1695 L/h
Baseline time-varying clearance0.369 L/h0.1845–0.5535 L/h
Baseline central distribution volume6.7 L3.35–10.05 L
Intercompartmental clearance0.0405 L/h0.02025–0.06075 L/h
Peripheral distribution volume5.1 L2.55–7.65 L

Expected readouts

Central inotuzumab ozogamicin · Exposure (AUC) (ng*h/mL) · Total clearance · Clearance desensitization rate

Adjustable model parameters

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More key parameters (1)

How the model represents the biology

A two-compartment population PK model for inotuzumab ozogamicin with linear and time-dependent clearance and clinically relevant body-size and disease covariates.

How do distribution, covariates, and time-dependent clearance shape ADC exposure?Intravenous inotuzumab ozogamicin enters a central ADC pool, exchanges with a peripheral pool, and undergoes baseline plus exponentially decaying clearance. Body size and disease covariates alter disposition, while central concentration accumulates as exposure.BIOLOGY OVERVIEWHow do distribution, covariates, and time-dependent clearance shape ADC exposure?IV ADC inputInotuzumab ozogamicinCentral ADC exposurePlasma amount andconcentrationPeripheral ADCReversible distributionTime-dependentclearanceBaseline plus decayingcomponentClinical covariatesBody size and disease factorsCumulative ADCexposureCentral concentration integralPRIMARY READOUTSCentral ADC concentrationCentral ADC concentrationCumulative exposureCumulative exposureTotal clearanceTotal clearanceClearance-decay rateClearance-decay rate

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

Model scope: CD22 binding, internalization, calicheamicin release, tumor-cell killing, efficacy, toxicity, and free-payload kinetics are not represented.

Modeled relationships (6)
  • IV ADC input → Central ADC exposure: IV input (flow)
  • Central ADC exposure ↔ Peripheral ADC: distribution (reversible exchange)
  • Central ADC exposure → Time-dependent clearance: CL1 + CL2(t) (loss)
  • Clinical covariates → Time-dependent clearance: scales CL (modulation)
  • Clinical covariates → Central ADC exposure: scales volume (modulation)
  • Central ADC exposure → Cumulative ADC exposure: integrates C (production)

Modeled relationships: IV ADC input to Central ADC exposure: IV input (flow); Central ADC exposure reversibly exchanges with Peripheral ADC: distribution (reversible exchange); Central ADC exposure to Time-dependent clearance: CL1 + CL2(t) (loss); Clinical covariates to Time-dependent clearance: scales CL (modulation); Clinical covariates to Central ADC exposure: scales volume (modulation); Central ADC exposure to Cumulative ADC exposure: integrates C (production).

Primary readouts: Central ADC concentration; Cumulative exposure; Total clearance; Clearance-decay rate.

Found a scientific issue? Email helpdesk@unibiointelligence.com with model ID garrett_2019_inotuzumab_ozogamicin_poppk.

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

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