A translational physiologically-based pharmacokinetic model for MMAE-based antibody-drug conjugates DOI Creative Commons
Hsuan‐Ping Chang, Dhaval K. Shah

Journal of Pharmacokinetics and Pharmacodynamics, Год журнала: 2025, Номер 52(3)

Опубликована: Май 5, 2025

Abstract The objective of this work was to develop a translational physiologically-based pharmacokinetic (PBPK) model for antibody-drug conjugates (ADCs), using monomethyl auristatin E (MMAE)-based ADCs. A previously established dual-structured whole-body PBPK MMAE-based ADCs in mice scaled higher species (i.e., rats and monkeys) humans. Species-specific physiological drug-related parameters the payload antibody backbone were obtained from literature. Parameters associated with release, including deconjugation rate, optimized an allometric scaling approach, degradation rate adjusted account enhanced clearance due conjugation across different species. predicted PK profiles various ADC analytes rats, monkeys, humans reasonably well. suggested decreased species, whereas effects on more pronounced presented here may enable prediction analyte at site-of-action, offering valuable insights development exposure-response relationships modeling framework can also serve as platform other

Язык: Английский

Evaluation of prompt engineering strategies for pharmacokinetic data analysis with the ChatGPT large language model DOI

Euibeom Shin,

Murali Ramanathan

Journal of Pharmacokinetics and Pharmacodynamics, Год журнала: 2023, Номер 51(2), С. 101 - 108

Опубликована: Ноя. 11, 2023

Язык: Английский

Процитировано

13
Drug product formulation and fill/finish manufacturing process considerations for AAV-based genomic medicines DOI

Madhura Som,

Benson Gikanga,

Varna Kanapuram

и другие.

Journal of Pharmaceutical Sciences, Год журнала: 2024, Номер 113(7), С. 1711 - 1725

Опубликована: Апрель 1, 2024

Язык: Английский

Процитировано

5
A translational physiologically-based pharmacokinetic model for MMAE-based antibody-drug conjugates DOI Creative Commons
Hsuan‐Ping Chang, Dhaval K. Shah

Journal of Pharmacokinetics and Pharmacodynamics, Год журнала: 2025, Номер 52(3)

Опубликована: Май 5, 2025

Abstract The objective of this work was to develop a translational physiologically-based pharmacokinetic (PBPK) model for antibody-drug conjugates (ADCs), using monomethyl auristatin E (MMAE)-based ADCs. A previously established dual-structured whole-body PBPK MMAE-based ADCs in mice scaled higher species (i.e., rats and monkeys) humans. Species-specific physiological drug-related parameters the payload antibody backbone were obtained from literature. Parameters associated with release, including deconjugation rate, optimized an allometric scaling approach, degradation rate adjusted account enhanced clearance due conjugation across different species. predicted PK profiles various ADC analytes rats, monkeys, humans reasonably well. suggested decreased species, whereas effects on more pronounced presented here may enable prediction analyte at site-of-action, offering valuable insights development exposure-response relationships modeling framework can also serve as platform other

Язык: Английский

Процитировано

0