Rituximab effect and B-cell recovery in pediatric nephrotic syndrome

375 mg/m2 x2 weekly

Conditional deterministic K-PD calculation at fixed source estimates; no population intervals or individual relapse prediction.

Readouts

CD19 b cell count · cells/uL

Absolute conditional CD19+ B-cell count.

B cell recovery relative to model baseline · dimensionless

Count divided by Kin/Kout; one is the untreated model equilibrium.

Latent rituximab effect amount · mg

Unmeasured K-PD effect coordinate; not plasma concentration.

Effective half maximal effect amount · mg

ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.

Study purpose

• How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?

Assumptions

• Conditional fixed-effect K-PD calculations; no original population fit, random effects, residual error, prediction intervals or complete paper reproduction.
• A1_mg is a latent rituximab effect amount, not a measured plasma concentration. The model has two biological states plus a separate clock.
• The observed clinical protocol was two weekly IV doses of 375 mg/m2, capped at 500 mg. Presets also include distinct theoretical simulation regimens, including 750 mg/m2; the clinical cap is not applied to those theoretical arms.
• Preset doses are fixed absolute mg derived, where applicable, from BSA 0.82 m2. Editing IgA does not change doses; BSA is inspection-only. Instantaneous latent-amount additions approximate day-scale dosing; infusion durations were not reported.
• Monthly and every-two-month schedules use 30-day and 60-day intervals. These are conditional calendar approximations.
• IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.
• Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.
• B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.
• The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.
• Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable.