modelPegaspargase

Diagram of Pegaspargase

Extends from Pharmacolibrary.Drugs.ATC.L.L01XX24.

Information

name:Pegaspargase
ATC code:L01XX24
route:intravenous
compartments:1
dosage:2500mg
volume of distribution:1.86L
clearance:0.167L/h/m2
other parameters in model implementation

Pegaspargase is a pegylated form of the enzyme L-asparaginase, used as an antineoplastic agent in the treatment of acute lymphoblastic leukemia (ALL) in pediatric and adult patients. It depletes asparagine, an amino acid essential to leukemic cells but not to normal cells, leading to selective cytotoxicity. Pegylation extends the half-life and reduces immunogenicity compared to native L-asparaginase. Pegaspargase is approved for clinical use in several countries including the US and EU.

Pharmacokinetics

Pharmacokinetic parameters reported in pediatric and adolescent patients with ALL (median age ~10 years) after single intravenous dose 2500 IU/m2.

References

  1. Douer, D, et al., & Avramis, VI (2007). Pharmacodynamics and safety of intravenous pegaspargase during remission induction in adults aged 55 years or younger with newly diagnosed acute lymphoblastic leukemia. Blood 109(7) 2744–2750. DOI:10.1182/blood-2006-07-035006 PUBMED:https://pubmed.ncbi.nlm.nih.gov/17132721

  2. Würthwein, G, et al., & Boos, J (2021). Population Pharmacokinetics of PEGylated Asparaginase in Children with Acute Lymphoblastic Leukemia: Treatment Phase Dependency and Predictivity in Case of Missing Data. European journal of drug metabolism and pharmacokinetics 46(2) 289–300. DOI:10.1007/s13318-021-00670-8 PUBMED:https://pubmed.ncbi.nlm.nih.gov/33595793

  3. Würthwein, G, et al., & Boos, J (2017). Population Pharmacokinetics to Model the Time-Varying Clearance of the PEGylated Asparaginase Oncaspar. European journal of drug metabolism and pharmacokinetics 42(6) 955–963. DOI:10.1007/s13318-017-0410-5 PUBMED:https://pubmed.ncbi.nlm.nih.gov/28349335

Parameters

TypeNameDefaultDescription
Modelica.Units.SI.Massweight (from PK_1C)75patient weight (kg)
Modelica.Units.SI.SpecificVolumeVdPerKg (from PK_1C)0.9Volume of distribution (L/kg)
Modelica.Units.SI.MassFractionF (from PK_1C)0.8bioavailiability (0-1)
Pharmacolibrary.Types.ClearanceCl (from PK_1C)20clearance
Modelica.Units.SI.TimeadminTime (from PK_1C)60first administration time (s)
Modelica.Units.SI.TimeadminDuration (from PK_1C)600administration duration (s)
Modelica.Units.SI.TimeadminPeriod (from PK_1C)8*60*60period of administration (default 8 hours)(s)
Pharmacolibrary.Types.MassadminMass (from PK_1C)1000administration mass (mg)
IntegeradminCount (from PK_1C)8number of dose administered (1)
Pharmacolibrary.Types.VolumeVd (from PK_1C)VdPerKg*weightVolume of distribution (m3)
Pharmacolibrary.Types.MassConcentrationCmin (from PK_1C)0.004minimal therapeutic range
Pharmacolibrary.Types.MassConcentrationCmax (from PK_1C)0.008minimal therapeutic range
Pharmacolibrary.Types.MassConcentrationCtox_peak (from PK_1C)0.012toxicity peak level
Pharmacolibrary.Types.MassConcentrationCtox_trough (from PK_1C)0.006toxicity trough level

Connectors

TypeNameDefaultDescription
Types.ConcentrationOutputC_central (from PK_1C)
Interfaces.ConcentrationPort_bcentralCPort (from PK_1C)

Components

TypeNameDefaultDescription
Pharmacokinetic.NoPerfusedTissueCompartmentcentral (from PK_1C)
Pharmacokinetic.ClearanceDrivenEliminationelim (from PK_1C)
Sources.PeriodicDoseperiodicDose (from PK_1C)
Modelica.Units.SI.Timet1_2 (from PK_1C)elimination half-life

Revisions

  • 06/2025 Tomas Kulhanek, generated model from data extracted from PUBMED, DrugBank and LLM(GPT4.1)