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Rituximab exposure and CD19-positive B-cell dynamics

Compare two specified serum-exposure and blood CD19-positive B-cell reference cases with distinct empirical relationships. Cumulative exposure is tracked separately and does not drive feedback.

Pharmacokinetic–pharmacodynamic modelling in a clinical pilot study of rituximab in multiple sclerosis: Towards personalized dosing interval ↗

British Journal of Clinical Pharmacology

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MODEL IN MOTION 18 sec

How does rituximab exposure connect with CD19-cell depletion and recovery?

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Fixed serum exposure and CD19 context A

Fixed post-administration serum rituximab and blood CD19 context, with explicit initial states, constant kinetic coefficients and separate physical accounting.

0–200 day

Scenario details

Fixed serum exposure and CD19 context A

Fixed post-administration serum rituximab and blood CD19 context, with explicit initial states, constant kinetic coefficients and separate physical accounting.

Readouts

Rituximab concentration · mg/L
Retained explicit state alias or conditional coefficient echo
CD19 · cell/millimeter^3
Retained explicit state alias or conditional coefficient echo
Exposure (AUC) · mg*day/L
Accumulated serum concentration AUC
Accounted drug concentration · mg/L
Separate drug concentration budget; equals supplied C(0)
Accounted cell count · cell/millimeter^3
Separate cell budget; equals supplied L(0)

Study purpose

  • How do the model's key biological readouts change under fixed serum exposure and cd19 context a?

Assumptions

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

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Simulation time
day
day
200 → 168

Time between reported samples.

day

1 change · Variation 1

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Biology

Two supplied deterministic serum concentration and blood CD19 contexts, with distinct empirical coupling coefficients, physical drug and cell budgets and nonfeedback AUC.

Two supplied deterministic serum concentration and blood CD19 contexts, with distinct empirical coupling coefficients, physical drug and cell budgets and nonfeedback AUC.

Model details

7 parameters · 9 states · 9 equations · 29 derived outputs

Classification & API access
Therapeutic
Rituximab
Modality
Monoclonal antibody
Target
CD20 / MS4A1
Disease / scope
Multiple sclerosis
ParameterDefaultUnitDescription
Baseline B-cell concentrationL0_cells_mm3199.57cell/mm³Supplied fixed baseline CD19 count controlling constant production; no population distribution is implemented.
Apparent distribution volumeV_l2.85049576986599LFixed apparent volume annotation used only in the nominal initial concentration readout; it never resets the explicit initial state.
Systemic clearancecl_day0.0303743678894691/dayFirst-order nonspecific serum concentration-loss rate, not volumetric clearance.
Rituximab dosedose_mg1000mgFixed nominal starting amount annotation, not an executable dose or editable administration control.
Concentration-dependent B-cell depletion ratekdeg1_mm3_mg_day0.00302462114205076mm³/(cell·day)Coefficient of C times blood CD19 count in concentration loss; physical unit inferred from the equation despite the stable historical key.
Exposure-dependent B-cell depletion ratekdeg2_l_mg_day0.0031257285864225L/(mg·day)Coefficient of C times blood CD19 count in cell depletion; distinct from concentration-loss coupling.
Turnover loss ratekout_day0.000410370016781721/dayNatural cell-turnover rate; production is baseline times turnover.

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