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Theophylline theo_md Multiple-Dose Validation

Dataset

  • Source: theo_md from nlmixr2data (GPL >= 3)
  • Columns: ID, TIME, DV, AMT, EVID, CMT, WT

Purpose

Stress test event handling and replay under multiple-dose designs: - Multiple dosing records per subject - Mixed dose and observation records - Long time horizons - Duplicated times and missing DV tolerance

Model

One-compartment oral PK with first-order absorption.

Fixed parameters (no fitting): | Parameter | Value | Unit | |-----------|-------|------| | Ka | 1.59 | 1/hr | | CL | 2.75 | L/hr | | V | 31.8 | L |

Dose Handling

  • All records with AMT > 0 are interpreted as dosing events
  • Dose unit rule is explicit and recorded in metadata:
  • If AMT < 50: treat as mg/kg and multiply by WT
  • Else: treat as mg

Outputs

  • One execution artifact per subject: subj_<id>.json
  • Metrics JSON with per-subject: id, wt, dose_unit_rule, dose_events, rmse

Running

# From repository root
julia docs/examples/real_world_validation/datasets/theophylline_theo_md/run.jl
julia docs/examples/real_world_validation/datasets/theophylline_theo_md/validate.jl