modelR03DA20

Extends from Pharmacokinetic.Models.PK_1C_enteral.

Information

name:CombinationsOfXanthines
ATC code:R03DA20
route:oral
compartments:1
dosage:240mg
volume of distribution:0.5L
clearance:0.04L/kg/h
other parameters in model implementation

Combinations of xanthines, such as theophylline with other bronchodilators (for example, etofylline or diprophylline), are used primarily in the management of asthma and chronic obstructive pulmonary disease (COPD) to relax bronchial smooth muscle and relieve bronchospasm. These combinations have been largely replaced by newer agents but may still be used in some countries for specific patient populations.

Pharmacokinetics

Pharmacokinetic parameters were estimated based on the combination of theophylline and etofylline in adults after oral administration. Model parameters are adapted from standard theophylline PK studies in adults (mean values in healthy subjects), as no direct publication for the exact combination was found.

References

  1. Zandvliet, AS, et al., & Beijnen, JH (2005). Population pharmacokinetics of caffeine and its metabolites theobromine, paraxanthine and theophylline after inhalation in combination with diacetylmorphine. Basic & clinical pharmacology & toxicology 96(1) 71–79. DOI:10.1111/j.1742-7843.2005.pto960111.x PUBMED:https://pubmed.ncbi.nlm.nih.gov/15667599

  2. Straka, RJ, et al., & Walker, PF (1996). Predominance of slow acetylators of N-acetyltransferase in a Hmong population residing in the United States. Journal of clinical pharmacology 36(8) 740–747. DOI:10.1002/j.1552-4604.1996.tb04244.x PUBMED:https://pubmed.ncbi.nlm.nih.gov/8877679

  3. Koren, G, et al., & MacLeod, SM (1985). Theophylline pharmacokinetics in adolescent females following coadministration of oral contraceptives. Clinical and investigative medicine. Medecine clinique et experimentale 8(3) 222–226. PUBMED:https://pubmed.ncbi.nlm.nih.gov/4042465

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.TransferRateka (from PK_1C_enteral)0.016666666666666666first order absorption rate
Modelica.Units.SI.TimeTlag (from PK_1C_enteral)600delay between oral administration and absorption (default 10min)

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)