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Submitted: 15 Mar 2026
Revision: 23 May 2026
Accepted: 26 May 2026
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Med J Tabriz Uni Med Sciences. Inpress.
doi: 10.34172/mj.026.35373
  Abstract View: 12

Pharmacology

Policy Brief

Why do medicines exhibit variable responses across patients? Leveraging the PBPK (Physiologically Based Pharmacokinetic) modeling approach forpersonalized medicine

Marzieh Nosrati 1 ORCID logo, A. Ghasem Jouyban 2,3 ORCID logo, Bita Mesgarpour 1* ORCID logo

1 National Institute of Medical Research Development (NIMAD), Tehran, Iran
2 Pharmaceutical Analysis Research Center, Pharmaceutical Sciences Institute, Tabriz University of Medical Sciences, Tabriz, Iran
3 Pharmaceutical Sciences Group, Academy of Medical Sciences of the Islamic Republic of Iran, Tehran, Iran
*Corresponding Author: Email: bmesgarpour@gmail.com

Abstract

Background. Interindividual variability in response to medicines is a major challenge for healthcare systems. Although conventional clinical trials constitute the foundation of drug approval, their restricted populations, controlled conditions, and limited representation of special groups reduce their ability to predict real-world drug performance. Physiologically Based Pharmacokinetic (PBPK) modeling has emerged as a mechanistic approach that integrates physiological, biological, and molecular information to predict drug behavior across diverse populations and support precision-oriented healthcare decisions.

Methods. This article was developed based on scientific content presented by an expert in PBPK modeling and was complemented by a narrative review of international evidence and regulatory experience. Literature addressing applications of PBPK in the prediction of drug–drug interactions, dose optimization in special populations, regulatory decision-making, virtual populations, model-informed precision dosing, and personalized medicine was reviewed. Policy-relevant implementation considerations were also examined.

Results. PBPK modeling demonstrated broad applicability across all stages of the medicine lifecycle, including dose selection, prediction of drug–drug interactions, assessment of special populations, support for drug labeling decisions, and advancement of stratified and personalized medicine. Emerging evidence suggests that combining PBPK with real-world evidence, virtual twin concepts, and quantitative biological data may reduce uncertainty, improve therapeutic outcomes, minimize unnecessary clinical studies, and enhance patient safety. Regulatory experiences indicate an expanding role for PBPK in the development and evaluation of drugs.

Conclusion. PBPK modeling extends beyond a research tool and represents a promising decision-support approach for modern healthcare systems. Sustainable implementation requires strengthening scientific capacity, regulatory readiness, and data infrastructure.

Practical Implications. Investment in education, infrastructure, regulatory frameworks, and real-world data integration may facilitate broader implementation of PBPK-based approaches and support evidence-informed precision medicine.



How to cite this article: Nosrati M, Jouyban A.Ch, Mesgarpour B. Investigation of the reasons behind variability in response to medicines: Leveraging Physiologically Based Pharmacokinetic (PBPK) modeling approach for personalized medicine. Med J Tabriz Uni Med Sciences.2026; 48(4): doi:10.34172/mj.026.35373
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