Application of the relationship between pharmacokinetics and pharmacodynamics in drug development and therapeutic equivalence: a PEARRL review

  • Objectives: The objective of this review is to provide an overview of PK/PD models, focusing on drug-specific PK/PD models and highlighting their value-added in drug development and regulatory decision-making. Key findings: Many PK/PD models, with varying degrees of complexity and physiological understanding, have been developed to evaluate the safety and efficacy of drug products. In special populations (e.g. pediatrics), in cases where there is genetic polymorphism and in other instances where therapeutic outcomes are not well described solely by PK metrics, the implementation of PK/PD models is crucial to assure the desired clinical outcome. Since dissociation between the pharmacokinetic and pharmacodynamic profiles is often observed, it is proposed that physiologically-based pharmacokinetic (PBPK) and PK/PD models be given more weight by regulatory authorities when assessing the therapeutic equivalence of drug products. Summary: Modeling and simulation approaches already play an important role in drug development. While slowly moving away from “one-size fits all” PK methodologies to assess therapeutic outcomes, further work is required to increase confidence in PK/PD models in translatability and prediction of various clinical scenarios to encourage more widespread implementation in regulatory decision-making.

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Author:Ioannis Loisios-Konstantinidis, Rafael L.M. Paraiso, Nikoletta Fotaki, Mark McAllister, Rodrigo Cristofoletti, Jennifer B. DressmanGND
Document Type:Preprint
Date of Publication (online):2019/11/04
Year of first Publication:2019
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/04/15
Tag:bioequivalence; drug development; modeling & simulation; pharmacokinetics/ pharmacodynamics (PK/PD),; regulatory science; therapeutic equivalence
Page Number:53
First Page:1
Last Page:53
As part of the PEARRL ITN under Marie Sklodowska Curie actions EU Horizon 2020 guidlines, I submit for open access to the JWGU library repository the above scientific review article
Preprint, später in: Journal of Pharmacy and Pharmacology, 71(4), 699-723, 2019
Institutes:Biochemie, Chemie und Pharmazie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
Licence (German):License LogoDeutsches Urheberrecht