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Crenezumab PK and plasma Aβ turnover

Explore crenezumab exposure and plasma amyloid-beta turnover after the specified intravenous administrations. This reduced two-compartment model tracks drug and target amounts separately.

Pharmacokinetics and pharmacodynamic effect of crenezumab on plasma and cerebrospinal fluid beta-amyloid in patients with mild-to-moderate Alzheimer’s disease ↗

Alzheimer's Research & Therapy

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MODEL IN MOTION 18 sec

How does crenezumab dose change the modeled amyloid target pools?

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15 mg/kg IV every 28 days, bolus approximation

Specified drug-free start with reference target baselines, seven nmol boluses and fixed daily observations through day 168.

0–168 day

Scenario details

15 mg/kg IV every 28 days, bolus approximation

Specified drug-free start with reference target baselines, seven nmol boluses and fixed daily observations through day 168.

Readouts

Ccren · nM
Specified reduced-model physical amount, concentration, flux, partition or nonfeedback accounting quantity.
Free Aβ40 · pM
Specified reduced-model physical amount, concentration, flux, partition or nonfeedback accounting quantity.
Free Aβ42 · pM
Specified reduced-model physical amount, concentration, flux, partition or nonfeedback accounting quantity.
Accounted drug · nmol
Specified reduced-model physical amount, concentration, flux, partition or nonfeedback accounting quantity.
Accounted Aβ40 · nmol
Specified reduced-model physical amount, concentration, flux, partition or nonfeedback accounting quantity.

Study purpose

  • How do the model's key biological readouts change under 15 mg/kg iv every 28 days, bolus approximation?

Assumptions

  • Deterministic reduced serum-drug/plasma-target model only; no original patient fitting, sampled population, published figure reproduction or clinical efficacy prediction.
  • Central target turnover is modeled independently for Aβ40 and Aβ42. No target peripheral, CSF or brain state is included.
  • Free/complex target is an algebraic Michaelis–Menten partition under antibody excess; no measured kon/koff kinetics are implied.
  • All three histories use fixed 72.3 kg reference context and literal existing nmol boluses. The 145 kDa molar conversion is an authored assumption.
  • SC depot/F/Ka remain in the equations but are inactive in every selected IV history. No SC route result is assigned.
  • Power-normalized fixed weight scaling is a declared assumption. No age/GFR/sex covariate function is applied.
  • Seven new cumulative accounting observers and four existing exposure/clock observers do not feed back to the biological states. Separate drug and target ledgers retain nmol; target pM requires 0.001 × Vc conversion.
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Simulation time
day
day

Time between reported samples.

day

Starting settings · Variation 1

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Biology

Specified fixed IV histories with two-compartment drug PK, central target Michaelis–Menten turnover and separate drug/target ledgers.

Specified fixed IV histories with two-compartment drug PK, central target Michaelis–Menten turnover and separate drug/target ledgers.

Model details

20 parameters · 16 states · 16 equations · 42 derived outputs

Classification & API access
Therapeutic
Crenezumab
Modality
Monoclonal antibody
Target
Amyloid beta / APP, beta-amyloid, Abeta(1-40), Abeta(1-42)
Disease / scope
Alzheimer disease
ParameterDefaultUnitDescription
Bwt on clelBWT_on_CLel0.835—Specified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Bwt on clintBWT_on_CLint0.474—Specified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Bwt on vcentBWT_on_Vcent0.725—Specified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Elimination clearanceCLel_L_day0.159L/daySpecified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Internalization clearanceCLint_L_day1.01L/daySpecified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Fsc fractionFsc_fraction0.662—Specified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Absorption rate constantKa_1_day0.1611/daySpecified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Aβ40 dissociation constantKd_abeta40_nM12nMSpecified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Aβ42 dissociation constantKd_abeta42_nM9.37nMSpecified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Intercompartmental clearanceQ_L_day0.142L/daySpecified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Central distribution volumeVcent_L2.89LSpecified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
VperiphVperiph_L1.84LSpecified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Aβ40 baselineabeta40_baseline_pM142pMSpecified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Aβ40 degradation rateabeta40_kdeg_1_day1141/daySpecified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Aβ42 baselineabeta42_baseline_pM5.98pMSpecified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Aβ42 degradation rateabeta42_kdeg_1_day2871/daySpecified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Body weightbody_weight_kg72.3kgSpecified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Reference weightreference_weight_kg72.3kgSpecified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Zero abetazero_abeta_pm0pMSpecified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.
Zero amountzero_amount_nmol0nmolSpecified fixed coefficient or reference constant in the declared reduced serum-drug/plasma-target model.

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