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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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Autor principal: Mahmood, Iftekhar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
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
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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.
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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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