modelC10AX16
Extends from Pharmacokinetic.Models.PK_2C.
Information
| name: | Inclisiran | |
| ATC code: | C10AX16 | route: | subcutaneous |
| compartments: | 2 | |
| dosage: | 284 | mg |
| volume of distribution: | 500 | L |
| clearance: | 144 | L/h |
| other parameters in model implementation | ||
Inclisiran is a small interfering RNA (siRNA) drug that targets and degrades PCSK9 mRNA in the liver, leading to lower levels of LDL cholesterol. It is used in the treatment of hypercholesterolemia and is approved for use in adults with elevated LDL-C who are at high risk for cardiovascular events.
Pharmacokinetics
Pharmacokinetics in adult subjects with hypercholesterolemia or mixed dyslipidemia after a single subcutaneous dose.
References
Yamashita, S, et al., & Kajinami, K (2024). Efficacy, Safety, and Pharmacokinetics of Inclisiran in Japanese Patients: Results from ORION-15. Journal of atherosclerosis and thrombosis 31(6) 876–903. DOI:10.5551/jat.64454 PUBMED:https://pubmed.ncbi.nlm.nih.gov/38220186
Luo, Z, et al., & He, Y (2023). The clinical effects of inclisiran, a first-in-class LDL-C lowering siRNA therapy, on the LDL-C levels in Chinese patients with hypercholesterolemia. Journal of clinical lipidology 17(3) 392–400. DOI:10.1016/j.jacl.2023.04.010 PUBMED:https://pubmed.ncbi.nlm.nih.gov/37164838
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 |
| Pharmacolibrary.Types.Volume | Vdp (from PK_2C) | VdpPerKg*weight | Volume of distribution (m3) |
| Modelica.Units.SI.SpecificVolume | VdpPerKg (from PK_2C) | 0.9 | Volume of distribution peripheral(l/kg) |
| Pharmacolibrary.Types.Clearance | k12 (from PK_2C) | 1 | intercompartmental C-P clearance |
| Pharmacolibrary.Types.Clearance | k21 (from PK_2C) | 1 | intercompartmental P-C clearance |
Connectors
| Type | Name | Default | Description |
|---|---|---|---|
| Types.ConcentrationOutput | C_central (from PK_1C) | ||
| Interfaces.ConcentrationPort_b | centralCPort (from PK_1C) | ||
| Interfaces.ConcentrationPort_b | peripheralCPort (from PK_2C) | ||
| Pharmacolibrary.Types.ConcentrationOutput | C_peripheral1 (from PK_2C) |
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 | |
| Pharmacolibrary.Pharmacokinetic.TransferFirstOrderNonSym | transfer (from PK_2C) | ||
| Pharmacolibrary.Pharmacokinetic.NoPerfusedTissueCompartment | peripheral (from PK_2C) |
Revisions
- 06/2025 Tomas Kulhanek, generated model from data extracted from PUBMED, DrugBank and LLM(GPT4.1)