The Perks and Drawbacks of Physiologically-Based Pharmacokinetic Modeling
Main Article Content
Abstract
Physiologically-based pharmacokinetic (PBPK) models use a mechanistic approach to integrate physiological parameters, physicochemical drug properties, and biochemical processes by means of mathematical equations to predict the concentration of a drug over time in blood and tissues. These models represent a robust tool for the pharmaceutical sciences, but also applications in chemical risk assessment for drugs and chemicals of forensic interest or in occupational hazards have been explored over the last decade. Much like other computational tools, PBPK models’ application face challenges concerning validity, transparency and lack of collaboration between professionals in different fields. The potential uses and challenges of PBPK modeling are discussed, as well as some ways to address the latter.
Article Details
How to Cite
QUIJANO-MATEOS, Alejandra.
The Perks and Drawbacks of Physiologically-Based Pharmacokinetic Modeling.
Medical Research Archives, [S.l.], v. 10, n. 9, sep. 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2944>. Date accessed: 05 nov. 2024.
doi: https://doi.org/10.18103/mra.v10i9.2944.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Espié P, Tytgat D, Sargentini-Maier ML, Poggesi I, Watelet JB. Physiologically based pharmacokinetics (PBPK). Drug Metab Rev. 2009;41(3):391-407. doi:10.1080/10837450902891360
2. Jones HM, Gardner IB, Watson KJ. Modelling and PBPK simulation in drug discovery. AAPS J. 2009;11(1):155-166. doi:10.1208/s12248-009-9088-1
3. Zhuang X, Lu C. PBPK modeling and simulation in drug research and development. Acta Pharm Sin B. 2016;6(5):430-440. doi:10.1016/J.APSB.2016.04.004
4. Poulin P, Burczynski FJ, Haddad S. The Role of Extracellular Binding Proteins in the Cellular Uptake of Drugs: Impact on Quantitative In Vitro-to-In Vivo Extrapolations of Toxicity and Efficacy in Physiologically Based Pharmacokinetic-Pharmacodynamic Research. J Pharm Sci. 2016;105(2):497-508. doi:10.1002/JPS.24571
5. Jones HM, Mayawala K, Poulin P. Dose selection based on physiologically based pharmacokinetic (PBPK) approaches. AAPS J. 2013;15(2):377-387. doi:10.1208/s12248-012-9446-2
6. Templeton IE, Jones NS, Musib L. Pediatric Dose Selection and Utility of PBPK in Determining Dose. AAPS J. 2018;20(2). doi:10.1208/s12248-018-0187-8
7. Johnson TN, Rostami-Hodjegan A. Resurgence in the use of physiologically based pharmacokinetic models in pediatric clinical pharmacology: Parallel shift in incorporating the knowledge of biological elements and increased applicability to drug development and clinical practice. Paediatr Anaesth. 2011;21(3):291-301. doi:10.1111/j.1460-9592.2010.03323.x
8. Wu F, Shah H, Li M, et al. Biopharmaceutics Applications of Physiologically Based Pharmacokinetic Absorption Modeling and Simulation in Regulatory Submissions to the U.S. Food and Drug Administration for New Drugs. AAPS J. 2021;23(2). doi:10.1208/s12248-021-00564-2
9. Sychterz C, Galetin A, Taskar KS. When special populations intersect with drug–drug interactions: Application of physiologically-based pharmacokinetic modeling in pregnant populations. Biopharm Drug Dispos. 2021;42(4):160-177. doi:10.1002/bdd.2272
10. Lu G, Abduljalil K, Jamei M, N. Johnson T, Soltani H, Rostami-Hodjegan A. Physiologically-based Pharmacokinetic (PBPK) Models for Assessing the Kinetics of Xenobiotics during Pregnancy: Achievements and Shortcomings. Curr Drug Metab. 2012;13(6):695-720. doi:10.2174/138920012800840374
11. Ke AB, Greupink R, Abduljalil K. Drug dosing in pregnant women: Challenges and opportunities in using physiologically based pharmacokinetic modeling and simulations. CPT Pharmacometrics Syst Pharmacol. 2018;7(2):103-110. doi:10.1002/psp4.12274
12. Wang K, Jiang K, Wei X, Li Y, Wang T, Song Y. Physiologically Based Pharmacokinetic Models Are Effective Support for Pediatric Drug Development. AAPS PharmSciTech. 2021;22(6). doi:10.1208/s12249-021-02076-w
13. Bravo-Gómez ME, Camacho-García LN, Castillo-Alanís LA, Mendoza-Meléndez MÁ, Quijano-Mateos A. Revisiting a physiologically based pharmacokinetic model for cocaine with a forensic scope. Toxicol Res (Camb). 2019;8(3):432-446. doi:10.1039/C8TX00309B
14. Andersen ME. Development of physiologically based pharmacokinetic and physiologically based pharmacodymamic models for applications in toxicology and risk assessment. Toxicol Lett. 1995;79(1-3):35-44.
doi:10.1016/0378-4274(95)03355-O
15. Huang SM. PBPK as a tool in regulatory review. Biopharm Drug Dispos. 2012;33(2):51-52. doi:10.1002/bdd.1777
16. Andersen ME. Toxicokinetic modeling and its applications in chemical risk assessment. Toxicol Lett. 2003;138(1-2):9-27. doi:10.1016/s0378-4274(02)00375-2
17. Poulin P. Drug distribution to human tissues: Prediction and examination of the basic assumption in in vivo pharmacokinetics-pharmacodynamics (PK/PD) research. J Pharm Sci. 2015;104(6):2110-2118. doi:10.1002/jps.24427
18. Ings RMJ. Interspecies scaling and comparisons in drug development and toxicokinetics. Xenobiotica. 1990;20(11):1201-1231. doi:10.3109/00498259009046839
19. Sayre RR, Wambaugh JF, Grulke CM. Database of pharmacokinetic time-series data and parameters for 144 environmental chemicals. Sci Data 2020 71. 2020;7(1):1-10. doi:10.1038/s41597-020-0455-1
20. An F, Qu Y, Liu X, Zhong R, Luo Y. Organ-on-a-chip: New platform for biological analysis. Anal Chem Insights. 2015;10(1):39-45. doi:10.4137/ACI.S28905
21. Yang Y, Chen Y, Wang L, et al. PBPK Modeling on Organs-on-Chips: An Overview of Recent Advancements. Front Bioeng Biotechnol. 2022;10. doi:10.3389/FBIOE.2022.900481
22. McLanahan ED, El-Masri HA, Sweeney LM, et al. Physiologically based pharmacokinetic model use in risk assessment–Why being published is not enough. Toxicol Sci. 2012;126(1):5-15. doi:10.1093/toxsci/kfr295
23. Fairman K, Li M, Kabadi S V., Lumen A. Physiologically based pharmacokinetic modeling: A promising tool for translational research and regulatory toxicology. Curr Opin Toxicol. 2020;23-24:17-22. doi:10.1016/j.cotox.2020.03.001
24. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research. Physiologically Based Pharmacokinetic Analyses — Format and Content Guidance for Industry.; 2018. https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
25. EMA. Guideline on the Reporting of Physiologically Based Pharmacokinetic (PBPK) Modelling and Simulation. Vol EMA/CHMP/4. European Medecines Agency; 2018. www.ema.europa.eu/contact
26. OECD. Guidance document on the characterization, validation and reporting of Physiologycally Based Kinetic (PBPK) models for regulatory purposes. In: OECD Series on Testing and Assessment. Vol No. 331. Environment, Healtd and Safety, Environment Directorate; 2021:13-101. www.oecd.org/chemicalsafety/
27. Tan YM, Chan M, Chukwudebe A, et al. PBPK model reporting template for chemical risk assessment applications. Regul Toxicol Pharmacol. 2020;115(104691):1-14. doi:10.1016/j.yrtph.2020.104691
28. Jean D, Naik K, Milligan L, et al. Development of best practices in physiologically based pharmacokinetic modeling to support clinical pharmacology regulatory decision-making—A workshop summary. CPT Pharmacometrics Syst Pharmacol. 2021;10(11):1271-1275. doi:10.1002/psp4.12706
29. Tan YM, Worley RR, Leonard JA, Fisher JW. Challenges associated with applying physiologically based pharmacokinetic modeling for public health decision-making. Toxicol Sci. 2018;162(2):341-348. doi:10.1093/toxsci/kfy010
30. Lin W, Chen Y, Unadkat JD, Zhang X, Wu D, Heimbach T. Applications, Challenges, and Outlook for PBPK Modeling and Simulation: A Regulatory, Industrial and Academic Perspective. Pharm Res. Published online May 13, 2022. doi:10.1007/S11095-022-03274-2
2. Jones HM, Gardner IB, Watson KJ. Modelling and PBPK simulation in drug discovery. AAPS J. 2009;11(1):155-166. doi:10.1208/s12248-009-9088-1
3. Zhuang X, Lu C. PBPK modeling and simulation in drug research and development. Acta Pharm Sin B. 2016;6(5):430-440. doi:10.1016/J.APSB.2016.04.004
4. Poulin P, Burczynski FJ, Haddad S. The Role of Extracellular Binding Proteins in the Cellular Uptake of Drugs: Impact on Quantitative In Vitro-to-In Vivo Extrapolations of Toxicity and Efficacy in Physiologically Based Pharmacokinetic-Pharmacodynamic Research. J Pharm Sci. 2016;105(2):497-508. doi:10.1002/JPS.24571
5. Jones HM, Mayawala K, Poulin P. Dose selection based on physiologically based pharmacokinetic (PBPK) approaches. AAPS J. 2013;15(2):377-387. doi:10.1208/s12248-012-9446-2
6. Templeton IE, Jones NS, Musib L. Pediatric Dose Selection and Utility of PBPK in Determining Dose. AAPS J. 2018;20(2). doi:10.1208/s12248-018-0187-8
7. Johnson TN, Rostami-Hodjegan A. Resurgence in the use of physiologically based pharmacokinetic models in pediatric clinical pharmacology: Parallel shift in incorporating the knowledge of biological elements and increased applicability to drug development and clinical practice. Paediatr Anaesth. 2011;21(3):291-301. doi:10.1111/j.1460-9592.2010.03323.x
8. Wu F, Shah H, Li M, et al. Biopharmaceutics Applications of Physiologically Based Pharmacokinetic Absorption Modeling and Simulation in Regulatory Submissions to the U.S. Food and Drug Administration for New Drugs. AAPS J. 2021;23(2). doi:10.1208/s12248-021-00564-2
9. Sychterz C, Galetin A, Taskar KS. When special populations intersect with drug–drug interactions: Application of physiologically-based pharmacokinetic modeling in pregnant populations. Biopharm Drug Dispos. 2021;42(4):160-177. doi:10.1002/bdd.2272
10. Lu G, Abduljalil K, Jamei M, N. Johnson T, Soltani H, Rostami-Hodjegan A. Physiologically-based Pharmacokinetic (PBPK) Models for Assessing the Kinetics of Xenobiotics during Pregnancy: Achievements and Shortcomings. Curr Drug Metab. 2012;13(6):695-720. doi:10.2174/138920012800840374
11. Ke AB, Greupink R, Abduljalil K. Drug dosing in pregnant women: Challenges and opportunities in using physiologically based pharmacokinetic modeling and simulations. CPT Pharmacometrics Syst Pharmacol. 2018;7(2):103-110. doi:10.1002/psp4.12274
12. Wang K, Jiang K, Wei X, Li Y, Wang T, Song Y. Physiologically Based Pharmacokinetic Models Are Effective Support for Pediatric Drug Development. AAPS PharmSciTech. 2021;22(6). doi:10.1208/s12249-021-02076-w
13. Bravo-Gómez ME, Camacho-García LN, Castillo-Alanís LA, Mendoza-Meléndez MÁ, Quijano-Mateos A. Revisiting a physiologically based pharmacokinetic model for cocaine with a forensic scope. Toxicol Res (Camb). 2019;8(3):432-446. doi:10.1039/C8TX00309B
14. Andersen ME. Development of physiologically based pharmacokinetic and physiologically based pharmacodymamic models for applications in toxicology and risk assessment. Toxicol Lett. 1995;79(1-3):35-44.
doi:10.1016/0378-4274(95)03355-O
15. Huang SM. PBPK as a tool in regulatory review. Biopharm Drug Dispos. 2012;33(2):51-52. doi:10.1002/bdd.1777
16. Andersen ME. Toxicokinetic modeling and its applications in chemical risk assessment. Toxicol Lett. 2003;138(1-2):9-27. doi:10.1016/s0378-4274(02)00375-2
17. Poulin P. Drug distribution to human tissues: Prediction and examination of the basic assumption in in vivo pharmacokinetics-pharmacodynamics (PK/PD) research. J Pharm Sci. 2015;104(6):2110-2118. doi:10.1002/jps.24427
18. Ings RMJ. Interspecies scaling and comparisons in drug development and toxicokinetics. Xenobiotica. 1990;20(11):1201-1231. doi:10.3109/00498259009046839
19. Sayre RR, Wambaugh JF, Grulke CM. Database of pharmacokinetic time-series data and parameters for 144 environmental chemicals. Sci Data 2020 71. 2020;7(1):1-10. doi:10.1038/s41597-020-0455-1
20. An F, Qu Y, Liu X, Zhong R, Luo Y. Organ-on-a-chip: New platform for biological analysis. Anal Chem Insights. 2015;10(1):39-45. doi:10.4137/ACI.S28905
21. Yang Y, Chen Y, Wang L, et al. PBPK Modeling on Organs-on-Chips: An Overview of Recent Advancements. Front Bioeng Biotechnol. 2022;10. doi:10.3389/FBIOE.2022.900481
22. McLanahan ED, El-Masri HA, Sweeney LM, et al. Physiologically based pharmacokinetic model use in risk assessment–Why being published is not enough. Toxicol Sci. 2012;126(1):5-15. doi:10.1093/toxsci/kfr295
23. Fairman K, Li M, Kabadi S V., Lumen A. Physiologically based pharmacokinetic modeling: A promising tool for translational research and regulatory toxicology. Curr Opin Toxicol. 2020;23-24:17-22. doi:10.1016/j.cotox.2020.03.001
24. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research. Physiologically Based Pharmacokinetic Analyses — Format and Content Guidance for Industry.; 2018. https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
25. EMA. Guideline on the Reporting of Physiologically Based Pharmacokinetic (PBPK) Modelling and Simulation. Vol EMA/CHMP/4. European Medecines Agency; 2018. www.ema.europa.eu/contact
26. OECD. Guidance document on the characterization, validation and reporting of Physiologycally Based Kinetic (PBPK) models for regulatory purposes. In: OECD Series on Testing and Assessment. Vol No. 331. Environment, Healtd and Safety, Environment Directorate; 2021:13-101. www.oecd.org/chemicalsafety/
27. Tan YM, Chan M, Chukwudebe A, et al. PBPK model reporting template for chemical risk assessment applications. Regul Toxicol Pharmacol. 2020;115(104691):1-14. doi:10.1016/j.yrtph.2020.104691
28. Jean D, Naik K, Milligan L, et al. Development of best practices in physiologically based pharmacokinetic modeling to support clinical pharmacology regulatory decision-making—A workshop summary. CPT Pharmacometrics Syst Pharmacol. 2021;10(11):1271-1275. doi:10.1002/psp4.12706
29. Tan YM, Worley RR, Leonard JA, Fisher JW. Challenges associated with applying physiologically based pharmacokinetic modeling for public health decision-making. Toxicol Sci. 2018;162(2):341-348. doi:10.1093/toxsci/kfy010
30. Lin W, Chen Y, Unadkat JD, Zhang X, Wu D, Heimbach T. Applications, Challenges, and Outlook for PBPK Modeling and Simulation: A Regulatory, Industrial and Academic Perspective. Pharm Res. Published online May 13, 2022. doi:10.1007/S11095-022-03274-2