modelN02AA53
Extends from Pharmacokinetic.Models.PK_1C_enteral.
Information
| name: | HydromorphoneAndNaloxone | |
| ATC code: | N02AA53 | route: | oral |
| compartments: | 1 | |
| dosage: | 8 | mg |
| volume of distribution: | 4.0 | L |
| clearance: | 1150 | mL/min |
| other parameters in model implementation | ||
Hydromorphone and naloxone is a fixed-dose combination used for the management of severe pain that requires opioid analgesia with reduced risk of opioid-induced constipation. Hydromorphone is a potent opioid agonist, while naloxone is an opioid antagonist intended to counteract opioid side effects locally in the gut. The combination is approved and used in some countries (e.g., the EU) for chronic severe pain.
Pharmacokinetics
Pharmacokinetic parameters are estimated based on available data for the individual components and the fixed combination. No direct population PK studies for the combination tablet were found. Estimates are based on published data for hydromorphone and for orally administered naloxone in healthy adults.
References
Thigpen, JC, et al., & Harirforoosh, S (2019). Opioids: A Review of Pharmacokinetics and Pharmacodynamics in Neonates, Infants, and Children. European journal of drug metabolism and pharmacokinetics 44(5) 591–609. DOI:10.1007/s13318-019-00552-0 PUBMED:https://pubmed.ncbi.nlm.nih.gov/31006834
Vandenbossche, J, et al., & Franc, MA (2014). The effect of UGT2B7*2 polymorphism on the pharmacokinetics of OROS® hydromorphone in Taiwanese subjects. Journal of clinical pharmacology 54(10) 1170–1179. DOI:10.1002/jcph.305 PUBMED:https://pubmed.ncbi.nlm.nih.gov/24706503
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.TransferRate | ka (from PK_1C_enteral) | 0.016666666666666666 | first order absorption rate |
| Modelica.Units.SI.Time | Tlag (from PK_1C_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) |
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 |
Revisions
- 06/2025 Tomas Kulhanek, generated model from data extracted from PUBMED, DrugBank and LLM(GPT4.1)