modelM05BX04
Extends from Pharmacokinetic.Models.PK_2C.
Information
| name: | Denosumab | |
| ATC code: | M05BX04 | route: | subcutaneous |
| compartments: | 2 | |
| dosage: | 60 | mg |
| volume of distribution: | 2.5 | L |
| clearance: | 0.008 | L/h |
| other parameters in model implementation | ||
Denosumab is a fully human monoclonal antibody that inhibits RANK ligand (RANKL), a key mediator of osteoclast formation, function, and survival, thus reducing bone resorption and increasing bone mass. It is approved for the treatment of osteoporosis in postmenopausal women and men at increased risk of fractures, as well as for bone loss associated with certain cancers and for prevention of skeletal-related events in patients with bone metastases.
Pharmacokinetics
Pharmacokinetic parameters reported for adults (including postmenopausal women with osteoporosis) after subcutaneous administration of denosumab 60 mg.
References
Zhang, S, et al., & Jiang, Z (2024). Efficacy, Safety, and Population Pharmacokinetics of MW032 Compared With Denosumab for Solid Tumor-Related Bone Metastases: A Randomized, Double-Blind, Phase 3 Equivalence Trial. JAMA oncology 10(4) 448–455. DOI:10.1001/jamaoncol.2023.6520 PUBMED:https://pubmed.ncbi.nlm.nih.gov/38329745
Vogg, B, et al., & Sekhar, S (2024). Pharmacokinetics and pharmacodynamics of the proposed biosimilar denosumab GP2411 and reference denosumab in healthy males. Expert opinion on biological therapy 24(1-2) 91–100. DOI:10.1080/14712598.2024.2308645 PUBMED:https://pubmed.ncbi.nlm.nih.gov/38269652
Gibiansky, L, et al., & Pérez-Ruixo, JJ (2012). Population pharmacokinetic analysis of denosumab in patients with bone metastases from solid tumours. Clinical pharmacokinetics 51(4) 247–260. DOI:10.2165/11598090-000000000-00000 PUBMED:https://pubmed.ncbi.nlm.nih.gov/22420579
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)