modelS01XA23
Extends from Pharmacokinetic.Models.PK_2C_enteral.
Information
| name: | Sirolimus | |
| ATC code: | S01XA23 | route: | oral |
| compartments: | 2 | |
| dosage: | 2 | mg |
| volume of distribution: | 12 | L |
| clearance: | 2.16 | L/h |
| other parameters in model implementation | ||
Sirolimus, also known as rapamycin, is a macrolide immunosuppressant drug primarily used to prevent organ transplant rejection, particularly in kidney transplant recipients. It works by inhibiting the mammalian target of rapamycin (mTOR), leading to suppression of T-cell proliferation and activity. Approved by regulatory agencies including the FDA and EMA, sirolimus is also investigated for other immunosuppressive and antiproliferative indications.
Pharmacokinetics
Reported pharmacokinetics of oral sirolimus in adult renal transplant patients (n=31, mixed sex, mostly stable, with ongoing immunosuppressive co-medication). Population pharmacokinetic analysis; median values cited.
References
Zhang, Y, et al., & Li, X (2021). Population pharmacokinetics of sirolimus in Chinese adult liver transplant recipients: a retrospective study. Xenobiotica; the fate of foreign compounds in biological systems 51(12) 1408–1415. DOI:10.1080/00498254.2022.2025628 PUBMED:https://pubmed.ncbi.nlm.nih.gov/34983304
Wang, D, et al., & Li, Z (2019). Population pharmacokinetics of sirolimus in pediatric patients with kaposiform hemangioendothelioma: A retrospective study. Oncology letters 18(3) 2412–2419. DOI:10.3892/ol.2019.10562 PUBMED:https://pubmed.ncbi.nlm.nih.gov/31452734
Li, S, et al., & Wang, Y (2022). Population Pharmacokinetic Analysis and Dosing Optimization of Sirolimus in Children With Tuberous Sclerosis Complex. Journal of clinical pharmacology 62(8) 948–959. DOI:10.1002/jcph.2033 PUBMED:https://pubmed.ncbi.nlm.nih.gov/35094415
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)