modelA16AX16
Extends from Pharmacokinetic.Models.PK_1C.
Information
| name: | Givosiran | |
| ATC code: | A16AX16 | route: | subcutaneous |
| compartments: | 1 | |
| dosage: | 2.5 | mg |
| volume of distribution: | 11.3 | L |
| clearance: | 3.0 | L/h |
| other parameters in model implementation | ||
Givosiran is a small interfering RNA (siRNA) therapeutic aimed at the treatment of acute hepatic porphyrias (AHP). It reduces the production of aminolevulinic acid synthase 1 (ALAS1) in the liver, thereby lowering toxic heme intermediates. It is approved and marketed under the brand name Givlaari.
Pharmacokinetics
Pharmacokinetic profile in adults with acute hepatic porphyria following subcutaneous administration.
References
Melch, M, et al., & Robbie, GJ (2023). Population Pharmacokinetic Analysis of the RNAi Therapeutic Givosiran in Patients with Acute Hepatic Porphyria. Clinical pharmacokinetics 62(1) 89–99. DOI:10.1007/s40262-022-01197-0 PUBMED:https://pubmed.ncbi.nlm.nih.gov/36633811
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)