modelR03DX07

Extends from Pharmacokinetic.Models.PK_2C_enteral.

Information

name:Roflumilast
ATC code:R03DX07
route:oral
compartments:2
dosage:500mg
volume of distribution:2.9L
clearance:9.6L/h
other parameters in model implementation

Roflumilast is a selective phosphodiesterase-4 (PDE4) inhibitor used as an anti-inflammatory drug primarily in the treatment of severe chronic obstructive pulmonary disease (COPD) with a history of exacerbations. It is approved as an oral therapy to reduce the risk of COPD exacerbations.

Pharmacokinetics

Pharmacokinetic parameters in healthy adult volunteers after a single oral dose.

References

  1. Li, Q, et al., & Ding, L (2017). Pharmacokinetics of Roflumilast and Its Active Metabolite Roflumilast N-Oxide in Healthy Chinese Subjects After Single and Multiple Oral Doses. European journal of drug metabolism and pharmacokinetics 42(3) 371–381. DOI:10.1007/s13318-016-0343-4 PUBMED:https://pubmed.ncbi.nlm.nih.gov/27306372

  2. Han, M, et al., & Li, JT (2023). A Single-center, Open-label, Parallel Control Study Comparing the Pharmacokinetics and Safety of a Single Oral Dose of Roflumilast and Its Active Metabolite Roflumilast N-oxide in Healthy Chinese and Caucasian Volunteers. Clinical pharmacology in drug development 12(3) 314–323. DOI:10.1002/cpdd.1209 PUBMED:https://pubmed.ncbi.nlm.nih.gov/36484261

  3. Lahu, G, et al., & Facius, A (2010). Population pharmacokinetic modelling of roflumilast and roflumilast N-oxide by total phosphodiesterase-4 inhibitory activity and development of a population pharmacodynamic-adverse event model. Clinical pharmacokinetics 49(9) 589–606. DOI:10.2165/11536600-000000000-00000 PUBMED:https://pubmed.ncbi.nlm.nih.gov/20690782

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
Pharmacolibrary.Types.VolumeVdp (from PK_2C)VdpPerKg*weightVolume of distribution (m3)
Modelica.Units.SI.SpecificVolumeVdpPerKg (from PK_2C)0.9Volume of distribution peripheral(l/kg)
Pharmacolibrary.Types.Clearancek12 (from PK_2C)1intercompartmental C-P clearance
Pharmacolibrary.Types.Clearancek21 (from PK_2C)1intercompartmental P-C clearance
Pharmacolibrary.Types.TransferRateka (from PK_2C_enteral)0.016666666666666666first order absorption rate
Modelica.Units.SI.TimeTlag (from PK_2C_enteral)600delay between oral administration and absorption (default 10min)

Connectors

TypeNameDefaultDescription
Types.ConcentrationOutputC_central (from PK_1C)
Interfaces.ConcentrationPort_bcentralCPort (from PK_1C)
Interfaces.ConcentrationPort_bperipheralCPort (from PK_2C)
Pharmacolibrary.Types.ConcentrationOutputC_peripheral1 (from PK_2C)

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
Pharmacolibrary.Pharmacokinetic.TransferFirstOrderNonSymtransfer (from PK_2C)
Pharmacolibrary.Pharmacokinetic.NoPerfusedTissueCompartmentperipheral (from PK_2C)

Revisions

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