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Dabigatran exposure and empirical idarucizumab reversal in sheep

Two dabigatran amount pools, delayed coagulation response and a separately administered empirical reversal effect in fixed sheep research contexts.

Dabigatran pharmacokinetic-pharmacodynamic in sheep: Informing dose for anticoagulation during cardiopulmonary bypass ↗

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How does the modeled reversal intervention change clotting time in the paired sheep presets?

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dabigatran 4mgkg sheep pkpd

Fixed deterministic sheep PK/PD calculation with source-derived coefficients and explicitly specified inputs. Idarucizumab is an empirical dimensionless reversal effect; no individual fitted effects or population draws are recovered.

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Scenario details

dabigatran 4mgkg sheep pkpd

Fixed deterministic sheep PK/PD calculation with source-derived coefficients and explicitly specified inputs. Idarucizumab is an empirical dimensionless reversal effect; no individual fitted effects or population draws are recovered.

Readouts

Central conc · mg/L
Deterministic model-derived quantity in the stated physical unit.
Effect conc · mg/L
Deterministic model-derived quantity in the stated physical unit.
Rtime · min
Raw additive empirical R-time; negative values are outside physiological applicability and remain unclipped.
Accounted dabigatran · mg
Current dabigatran plus eliminated dabigatran, compared with delivered drug on the same event side.

Study purpose

  • How do the model's key biological readouts change under dabigatran 4mgkg sheep pkpd?

Assumptions

  • Interpret patterns within this model and starting configuration; do not treat them as clinical predictions or treatment recommendations.

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Time between reported samples.

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Biology

Two dabigatran amount pools, delayed coagulation response and a separately administered empirical reversal effect in fixed sheep research contexts.

Two dabigatran amount pools, delayed coagulation response and a separately administered empirical reversal effect in fixed sheep research contexts.

Model details

27 parameters · 6 states · 6 equations · 17 derived outputs

Classification & API access
Therapeutic
dabigatran and idarucizumab, idarucizumab
Modality
Antibody fragment
Target
dabigatran-associated coagulation response
Disease / scope
Healthy anesthetized sheep, fixed experimental histories
ParameterDefaultUnitDescription
Body weightbody_weight_kg34.42kgFixed source coefficient or explicitly specified research-context quantity.
Effect site concentration at half emaxce50_mg_l64.2mg/LFixed source coefficient or explicitly specified research-context quantity.
Standardized systemic clearancecl_std_l_min_70kg0.0453L/minFixed source coefficient or explicitly specified research-context quantity.
Clearance allometric exponentclearance_allometric_exp0.75—Fixed source coefficient or explicitly specified research-context quantity.
Circuit switch fixed offcpb_enabled0—Fixed inactive-circuit quantity; active-circuit behavior is outside this model scope.
Baseline r timee0_min0.681minFixed source coefficient or explicitly specified research-context quantity.
Effect site half time weight exponenteffect_half_time_allometric_exp0.25—Fixed source coefficient or explicitly specified research-context quantity.
Maximum effectemax_min180minFixed source coefficient or explicitly specified research-context quantity.
Eta CE50eta_ce500—Fixed log coefficient multiplier, used as exp(eta) in the selected context.
Eta clearanceeta_cl0—Fixed log coefficient multiplier, used as exp(eta) in the selected context.
Eta E0eta_e00—Fixed log coefficient multiplier, used as exp(eta) in the selected context.
Eta k idarucizumabeta_k_ida0—Fixed log coefficient multiplier, used as exp(eta) in the selected context.
Eta qeta_q0—Fixed log coefficient multiplier, used as exp(eta) in the selected context.
Eta distribution volume 1eta_v10—Fixed log coefficient multiplier, used as exp(eta) in the selected context.
Eta distribution volume 2eta_v20—Fixed log coefficient multiplier, used as exp(eta) in the selected context.
Hill coefficienthill_n1—Fixed source coefficient or explicitly specified research-context quantity.
Idarucizumab binding ratek_ida_per_min0.02181/minFixed source coefficient or explicitly specified research-context quantity.
Optional cpb pump flow clearanceq_cpb_l_min0L/minFixed inactive-circuit quantity; active-circuit behavior is outside this model scope.
Standardized intercompartmental clearanceq_std_l_min_70kg0.268L/minFixed source coefficient or explicitly specified research-context quantity.
Idarucizumab response slopeslope_ida_min_per_unit8.24minFixed source coefficient or explicitly specified research-context quantity.
Allometric standard weightstd_weight_kg70kgFixed source coefficient or explicitly specified research-context quantity.
Effect-compartment half-lifet12_keo_min1.04minFixed source coefficient or explicitly specified research-context quantity.
Paper target dabigatran concentrationtarget_concentration_mg_l5mg/LFixed source coefficient or explicitly specified research-context quantity.
Standardized central distribution volumev1_std_l_70kg2.94LFixed source coefficient or explicitly specified research-context quantity.
Standardized peripheral volumev2_std_l_70kg9.51LFixed source coefficient or explicitly specified research-context quantity.
Optional cpb circuit volumev_cpb_l1LFixed inactive-circuit quantity; active-circuit behavior is outside this model scope.
Volume allometric exponentvolume_allometric_exp1—Fixed source coefficient or explicitly specified research-context quantity.

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