Cemiplimab pharmacokinetics with time-varying clearance

Mean-covariate individual 3 mg/kg Q2W IV regimen

Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.

Readouts

Central conc · mg/L

Fixed-context model quantity in the stated physical unit.

Clearance ind · L/day

Fixed-context model quantity in the stated physical unit.

Exposure (AUC) · day*mg/L

Fixed-context model quantity in the stated physical unit.

Accounted cemiplimab · mg

Current central plus peripheral amount and integrated cumulative elimination.

Study purpose

• How do the model's key biological readouts change under mean-covariate individual 3 mg/kg q2w iv regimen?

Assumptions

• Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.
• Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.
• Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.
• The selected T50 reference branch has no categorical race prediction.
• AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.
• T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.
• Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.
• No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided.