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Physiologically based pharmacokinetic modeling of tapentadol in children to support pediatric dose selection

Zilong Wang1, Yujie Yang2, Zhihai Cao1

  • 1School of Pharmacy, Anhui Medical University, Hefei 230601, China; Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.

Journal of Pharmaceutical Sciences
|May 11, 2025
PubMed

Insights

This study developed a physiologically based pharmacokinetic (PBPK) model to establish safe and effective tapentadol dosing regimens for pediatric patients across all age groups. The model ensures accurate tapentadol dosage recommendations for children.

Area of Science:

  • Pharmacokinetics and Pharmacodynamics
  • Pediatric Pharmacology
  • Computational Modeling

Background:

  • Tapentadol is an effective opioid analgesic for moderate to severe pain unresponsive to non-opioid analgesics.
  • Optimizing pediatric dosing is crucial due to physiological differences affecting drug disposition.
  • Physiologically based pharmacokinetic (PBPK) modeling offers a robust approach for pediatric drug dosage refinement.

Purpose of the Study:

  • To develop and validate a PBPK model for tapentadol disposition in pediatric populations.
  • To characterize tapentadol pharmacokinetics (PK) across diverse pediatric age groups.
  • To establish refined, age-specific dosing strategies for tapentadol oral solution in children.

Main Methods:

  • An adult PBPK model was adapted for pediatric use by scaling anatomical and physiological parameters.
  • Model validation involved comparing simulated plasma concentrations against empirical data.
  • Dosages were translated from adult to pediatric populations, with weight-adjusted doses assessed for different age strata.

Main Results:

  • The PBPK model accurately predicted tapentadol PK parameters in pediatric populations, with a mean absolute prediction error (MAPE) below 0.45.
  • Predicted to observed PK parameter ratios for adults ranged from 0.80 to 1.40.
  • A validated fixed-dose regimen for tapentadol oral solution was established for children from 0 to 18 years.

Conclusions:

  • The developed PBPK model successfully characterized tapentadol disposition in pediatric patients.
  • The study provides evidence-based, fixed-dose recommendations for tapentadol oral solution across pediatric age groups.
  • Findings support the utility of PBPK modeling for optimizing pediatric drug dosing, especially for drugs with complex metabolic pathways.

Keywords:
ChildrenDosing selectionPhysiologically based pharmacokinetic (PBPK) modelingTapentadol

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