modelLumasiran
Extends from Pharmacolibrary.Drugs.ATC.A.A16AX18.
Information
| name: | Lumasiran | |
| ATC code: | A16AX18 | route: | subcutaneous |
| compartments: | 1 | |
| dosage: | 3 | mg |
| volume of distribution: | 0.3 | L |
| clearance: | 0.32 | L/h/kg |
| other parameters in model implementation | ||
Lumasiran is a small interfering RNA (siRNA) therapeutic indicated for the treatment of primary hyperoxaluria type 1 (PH1), a rare genetic disorder characterized by the overproduction of oxalate leading to kidney stones and renal failure. Approved by the FDA and EMA, it is administered subcutaneously and works by silencing the HAO1 gene to reduce hepatic glycolate oxidase production.
Pharmacokinetics
Pharmacokinetic parameters based on healthy adult volunteers and patients with primary hyperoxaluria type 1 after subcutaneous administration.
References
Michael, M, et al., & Magen, D (2023). Lumasiran for Advanced Primary Hyperoxaluria Type 1: Phase 3 ILLUMINATE-C Trial. American journal of kidney diseases : the official journal of the National Kidney Foundation 81(2) 145–155.e1. DOI:10.1053/j.ajkd.2022.05.012 PUBMED:https://pubmed.ncbi.nlm.nih.gov/35843439
Jeon, JY, et al., & Mitra, A (2022). Pharmacokinetic and Pharmacodynamic Modeling of siRNA Therapeutics - a Minireview. Pharmaceutical research 39(8) 1749–1759. DOI:10.1007/s11095-022-03333-8 PUBMED:https://pubmed.ncbi.nlm.nih.gov/35819583
Parameters
| Type | Name | Default | Description |
|---|---|---|---|
| Modelica.Units.SI.Mass | weight (from PK_1C) | 75 | patient weight (kg) |
| Modelica.Units.SI.SpecificVolume | VdPerKg (from PK_1C) | 0.9 | Volume of distribution (L/kg) |
| Modelica.Units.SI.MassFraction | F (from PK_1C) | 0.8 | bioavailiability (0-1) |
| Pharmacolibrary.Types.Clearance | Cl (from PK_1C) | 20 | clearance |
| Modelica.Units.SI.Time | adminTime (from PK_1C) | 60 | first administration time (s) |
| Modelica.Units.SI.Time | adminDuration (from PK_1C) | 600 | administration duration (s) |
| Modelica.Units.SI.Time | adminPeriod (from PK_1C) | 8*60*60 | period of administration (default 8 hours)(s) |
| Pharmacolibrary.Types.Mass | adminMass (from PK_1C) | 1000 | administration mass (mg) |
| Integer | adminCount (from PK_1C) | 8 | number of dose administered (1) |
| Pharmacolibrary.Types.Volume | Vd (from PK_1C) | VdPerKg*weight | Volume of distribution (m3) |
| Pharmacolibrary.Types.MassConcentration | Cmin (from PK_1C) | 0.004 | minimal therapeutic range |
| Pharmacolibrary.Types.MassConcentration | Cmax (from PK_1C) | 0.008 | minimal therapeutic range |
| Pharmacolibrary.Types.MassConcentration | Ctox_peak (from PK_1C) | 0.012 | toxicity peak level |
| Pharmacolibrary.Types.MassConcentration | Ctox_trough (from PK_1C) | 0.006 | toxicity trough level |
Connectors
| Type | Name | Default | Description |
|---|---|---|---|
| Types.ConcentrationOutput | C_central (from PK_1C) | ||
| Interfaces.ConcentrationPort_b | centralCPort (from PK_1C) |
Components
| Type | Name | Default | Description |
|---|---|---|---|
| Pharmacokinetic.NoPerfusedTissueCompartment | central (from PK_1C) | ||
| Pharmacokinetic.ClearanceDrivenElimination | elim (from PK_1C) | ||
| Sources.PeriodicDose | periodicDose (from PK_1C) | ||
| Modelica.Units.SI.Time | t1_2 (from PK_1C) | elimination half-life |
Revisions
- 06/2025 Tomas Kulhanek, generated model from data extracted from PUBMED, DrugBank and LLM(GPT4.1)