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A Simple Method for the Prediction of Human Concentration–Time Profiles and Pharmacokinetics of Antibody–Drug Conjugates (ADC) from Rats or Monkeys
Knowledge of human concentration–time profiles from animal data can be useful during early drug development. The objective of this study is to predict human concentration–time profiles of antibody–drug conjugates (ADCs) and subsequently predict pharmacokinetic parameters in humans from rats or monke...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219807/ https://www.ncbi.nlm.nih.gov/pubmed/35735361 http://dx.doi.org/10.3390/antib11020042 |
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author | Mahmood, Iftekhar |
author_facet | Mahmood, Iftekhar |
author_sort | Mahmood, Iftekhar |
collection | PubMed |
description | Knowledge of human concentration–time profiles from animal data can be useful during early drug development. The objective of this study is to predict human concentration–time profiles of antibody–drug conjugates (ADCs) and subsequently predict pharmacokinetic parameters in humans from rats or monkeys. Eight methods with different exponents of volume of distribution (0.8–1) as well as exponents of clearance (0.85), along with the exponents of volume of distribution for 5 ADCs, were used to predict human concentration–time profiles. The PK parameters were also scaled to humans from monkeys or rats using fixed exponents and compared with the PK parameters predicted from predicted human concentration–time profiles. The results of the study indicated that the exponent 0.9 and the combination of exponents of 0.9 and 0.8 (two exponents, 0.8 and 0.9, were used) were the best method to predict human concentration–time profiles and, subsequently, human PK parameters. The predicted PK parameters from fixed exponents were comparable with the predicted PK parameters estimated from human concentration–time profiles. The proposed methods are applicable to rats or monkeys with the same degree of accuracy. Overall, the proposed methods are robust, accurate, and cost- and time-effective. |
format | Online Article Text |
id | pubmed-9219807 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92198072022-06-24 A Simple Method for the Prediction of Human Concentration–Time Profiles and Pharmacokinetics of Antibody–Drug Conjugates (ADC) from Rats or Monkeys Mahmood, Iftekhar Antibodies (Basel) Article Knowledge of human concentration–time profiles from animal data can be useful during early drug development. The objective of this study is to predict human concentration–time profiles of antibody–drug conjugates (ADCs) and subsequently predict pharmacokinetic parameters in humans from rats or monkeys. Eight methods with different exponents of volume of distribution (0.8–1) as well as exponents of clearance (0.85), along with the exponents of volume of distribution for 5 ADCs, were used to predict human concentration–time profiles. The PK parameters were also scaled to humans from monkeys or rats using fixed exponents and compared with the PK parameters predicted from predicted human concentration–time profiles. The results of the study indicated that the exponent 0.9 and the combination of exponents of 0.9 and 0.8 (two exponents, 0.8 and 0.9, were used) were the best method to predict human concentration–time profiles and, subsequently, human PK parameters. The predicted PK parameters from fixed exponents were comparable with the predicted PK parameters estimated from human concentration–time profiles. The proposed methods are applicable to rats or monkeys with the same degree of accuracy. Overall, the proposed methods are robust, accurate, and cost- and time-effective. MDPI 2022-06-14 /pmc/articles/PMC9219807/ /pubmed/35735361 http://dx.doi.org/10.3390/antib11020042 Text en © 2022 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mahmood, Iftekhar A Simple Method for the Prediction of Human Concentration–Time Profiles and Pharmacokinetics of Antibody–Drug Conjugates (ADC) from Rats or Monkeys |
title | A Simple Method for the Prediction of Human Concentration–Time Profiles and Pharmacokinetics of Antibody–Drug Conjugates (ADC) from Rats or Monkeys |
title_full | A Simple Method for the Prediction of Human Concentration–Time Profiles and Pharmacokinetics of Antibody–Drug Conjugates (ADC) from Rats or Monkeys |
title_fullStr | A Simple Method for the Prediction of Human Concentration–Time Profiles and Pharmacokinetics of Antibody–Drug Conjugates (ADC) from Rats or Monkeys |
title_full_unstemmed | A Simple Method for the Prediction of Human Concentration–Time Profiles and Pharmacokinetics of Antibody–Drug Conjugates (ADC) from Rats or Monkeys |
title_short | A Simple Method for the Prediction of Human Concentration–Time Profiles and Pharmacokinetics of Antibody–Drug Conjugates (ADC) from Rats or Monkeys |
title_sort | simple method for the prediction of human concentration–time profiles and pharmacokinetics of antibody–drug conjugates (adc) from rats or monkeys |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219807/ https://www.ncbi.nlm.nih.gov/pubmed/35735361 http://dx.doi.org/10.3390/antib11020042 |
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