HematologyCardiovascular & coagulation PKPD

Dabigatran–idarucizumab reversal during cardiopulmonary bypass

Reference paper ↗

A PK/PD model coupling dabigatran systemic and bypass-circuit disposition to effect-site concentration and idarucizumab exposure during cardiopulmonary bypass.

Therapeutic
Dabigatran and idarucizumab
Modality
Antibody fragment
Target
Thrombin, Dabigatran
Disease
Preclinical anticoagulation reversal during cardiopulmonary bypass
Model type
PKPD

Complete model workspace

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Parameters
24
States
7
Equations
7
Derived outputs
58

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Starting configuration

CPB dabigatran and idarucizumab reversal

CPB dabigatran and idarucizumab reversal

How do bypass-circuit exchange and idarucizumab exposure change dabigatran concentration and effect-site reversal? Explore this biological starting configuration through Central dabigatran concentration, Dabigatran effect-site concentration, Bypass-circuit dabigatran concentration, Idarucizumab concentration, Mean bypass dabigatran concentration.

Starting result

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Starting configuration

Time: 0–1,440 minute; step 1

InputDefaultAvailable range
Standardized systemic clearance0.0509 L/minute0.02545–0.07635 L/minute
Standardized central distribution volume3.89 L1.945–5.835 L
Circuit flow rate1.82 L/min0.91–2.73 L/min
Idarucizumab clearance0.0394 L/min0.0197–0.0591 L/min
Idarucizumab loading dose50 mg/kg25–75 mg/kg

Expected readouts

Central dabigatran concentration · Effect-site concentration (mg/L) · Bypass circuit dabigatran concentration · Idarucizumab concentration · Mean bypass dabigatran concentration

Adjustable model parameters

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More key parameters (1)

How the model represents the biology

A PK/PD model coupling dabigatran systemic and bypass-circuit disposition to effect-site concentration and idarucizumab exposure during cardiopulmonary bypass.

How do protocol-driven dabigatran and idarucizumab exposures evolve during CPB?A timed protocol independently supplies dabigatran and idarucizumab. Dabigatran distributes between central, peripheral, and CPB-circuit pools and equilibrates with an effect-site concentration. Idarucizumab has separate exposure and clearance; the released equations do not couple it to dabigatran or the effect site.BIOLOGY OVERVIEWHow do protocol-driven dabigatran and idarucizumab exposures evolve during CPB?Timed protocol inputsSeparate drug-rate schedulesCentral dabigatranSystemic exposurePeripheral dabigatranReversible distributionCPB circuit poolGated pump exchangeEffect-siteconcentrationEquilibrates with central drugIdarucizumab exposureIndependent modeled amountSeparate clearancesNo modeled neutralizationcouplingPRIMARY READOUTSDabigatran concentrationDabigatran concentrationEffect-site concentrationEffect-site concentrationCPB circuit concentrationCPB circuit concentrationIdarucizumab concentrationIdarucizumab concentrationCPB mean dabigatranCPB mean dabigatran

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

Model scope: Idarucizumab binding or neutralization of dabigatran, an idarucizumab-to-effect-site influence, coagulation, and a reaction-time response are not present in the released equations.

Modeled relationships (7)
  • Timed protocol inputs → Central dabigatran: dabigatran rates (flow)
  • Timed protocol inputs → Idarucizumab exposure: idarucizumab rates (flow)
  • Central dabigatran ↔ Peripheral dabigatran: distribution (reversible exchange)
  • Central dabigatran ↔ CPB circuit pool: CPB exchange (reversible exchange)
  • Central dabigatran → Effect-site concentration: equilibration (modulation)
  • Central dabigatran → Separate clearances: dabigatran CL (loss)
  • Idarucizumab exposure → Separate clearances: idarucizumab CL (loss)

Modeled relationships: Timed protocol inputs to Central dabigatran: dabigatran rates (flow); Timed protocol inputs to Idarucizumab exposure: idarucizumab rates (flow); Central dabigatran reversibly exchanges with Peripheral dabigatran: distribution (reversible exchange); Central dabigatran reversibly exchanges with CPB circuit pool: CPB exchange (reversible exchange); Central dabigatran to Effect-site concentration: equilibration (modulation); Central dabigatran to Separate clearances: dabigatran CL (loss); Idarucizumab exposure to Separate clearances: idarucizumab CL (loss).

Primary readouts: Dabigatran concentration; Effect-site concentration; CPB circuit concentration; Idarucizumab concentration; CPB mean dabigatran.

Found a scientific issue? Email helpdesk@unibiointelligence.com with model ID eaton_2025_dabigatran_idarucizumab_sheep_cpb_pkpd.

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

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