modelC10AX11
Extends from Pharmacokinetic.Models.PK_2C.
Information
| name: | Mipomersen | |
| ATC code: | C10AX11 | route: | subcutaneous |
| compartments: | 2 | |
| dosage: | 200 | mg |
| volume of distribution: | 6.1 | L |
| clearance: | 5.3 | mL/h/kg |
| other parameters in model implementation | ||
Mipomersen is an antisense oligonucleotide inhibitor of apolipoprotein B-100 synthesis, used for the treatment of homozygous familial hypercholesterolemia to reduce LDL cholesterol. It was approved by the FDA but is not currently marketed in many regions, including the US, due to safety concerns.
Pharmacokinetics
Pharmacokinetic parameters reported in adult patients with homozygous familial hypercholesterolemia after subcutaneous administration.
References
Patel, N, & Hegele, RA (2010). Mipomersen as a potential adjunctive therapy for hypercholesterolemia. Expert opinion on pharmacotherapy 11(15) 2569–2572. DOI:10.1517/14656566.2010.512006 PUBMED:https://pubmed.ncbi.nlm.nih.gov/20707601
Li, Z, et al., & von Moltke, LL (2014). Pharmacokinetics, safety and tolerability of mipomersen in healthy Japanese volunteers and comparison with Western subjects. International journal of clinical pharmacology and therapeutics 52(4) 314–320. DOI:10.5414/CP201975 PUBMED:https://pubmed.ncbi.nlm.nih.gov/24548981
Li, Z, et al., & Boltje, I (2014). Lack of clinical pharmacodynamic and pharmacokinetic drug-drug interactions between warfarin and the antisense oligonucleotide mipomersen. Journal of cardiovascular pharmacology 64(2) 164–171. DOI:10.1097/FJC.0000000000000101 PUBMED:https://pubmed.ncbi.nlm.nih.gov/24691275
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)