modelSelinexor
Extends from Pharmacolibrary.Drugs.ATC.L.L01XX66.
Information
| name: | Selinexor | |
| ATC code: | L01XX66 | route: | oral |
| compartments: | 2 | |
| dosage: | 80 | mg |
| volume of distribution: | 125 | L |
| clearance: | 7.5 | L/h |
| other parameters in model implementation | ||
Selinexor is a selective inhibitor of nuclear export (SINE) that binds to and inhibits exportin 1 (XPO1). By blocking XPO1, selinexor leads to the nuclear retention and activation of tumor suppressor proteins, thereby causing cell cycle arrest and apoptosis in malignant cells. Selinexor is approved for the treatment of relapsed or refractory multiple myeloma and relapsed or refractory diffuse large B-cell lymphoma.
Pharmacokinetics
Pharmacokinetic model parameters for selinexor in adult patients with advanced solid tumors and hematologic malignancies. Parameters based on population pharmacokinetic analysis in relapsed/refractory multiple myeloma (mostly adults, both sexes).
References
Bader, JC, et al., & Xu, H (2021). Pharmacokinetics of Selinexor: The First-in-Class Selective Inhibitor of Nuclear Export. Clinical pharmacokinetics 60(8) 957–969. DOI:10.1007/s40262-021-01016-y PUBMED:https://pubmed.ncbi.nlm.nih.gov/33928519
Podar, K, et al., & Jagannath, S (2020). Selinexor for the treatment of multiple myeloma. Expert opinion on pharmacotherapy 21(4) 399–408. DOI:10.1080/14656566.2019.1707184 PUBMED:https://pubmed.ncbi.nlm.nih.gov/31957504
Rubinstein, MM, et al., & Makker, V (2021). A phase I open-label study of selinexor with paclitaxel and carboplatin in patients with advanced ovarian or endometrial cancers. Gynecologic oncology 160(1) 71–76. DOI:10.1016/j.ygyno.2020.10.019 PUBMED:https://pubmed.ncbi.nlm.nih.gov/33139041
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 |
| Pharmacolibrary.Types.TransferRate | ka (from PK_2C_enteral) | 0.016666666666666666 | first order absorption rate |
| Modelica.Units.SI.Time | Tlag (from PK_2C_enteral) | 600 | delay between oral administration and absorption (default 10min) |
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)