Importance of Target-mediated Drug Disposition (TMDD) of Small-molecule Compounds and its Impact on Drug Development | Dr. Guohua An

Importance of Target-mediated Drug Disposition (TMDD) of Small-molecule Compounds and its Impact on Drug Development | Dr. Guohua An

Target-mediated drug disposition (TMDD) is a term to describe a nonlinear pharmacokinetics (PK) phenomenon that is caused by high-affinity binding of a compound to its pharmacologic targets. As the interaction between drug and its pharmacologic target belongs to the process of pharmacodynamics (PD), TMDD can be viewed as a consequence of "PD affecting PK". Both large-molecule and small-molecule compounds can undergo TMDD. However, TMDD in large-molecule compounds is well known due to its high prevalence, while TMDD in small molecule compounds is more counter-intuitive and has been an overlooked area. Recognizing TMDD in small-molecule compounds is important, as the information can be leveraged to select the appropriate dose regimen, improve clinical trial design, as well as predict pharmacological target occupancy. This webinar summarizes the general pharmacokinetic features that facilitate the recognition of small-molecule TMDD, provides case examples of different classes of small-molecules exhibiting TMDD, highlights the importance of recognizing TMDD of small-molecule compounds during clinical development, and presenting the pharmacometric models that have been used to facilitate the quantitative understanding of small molecules exhibiting TMDD.

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Importance of Target-mediated Drug Disposition (TMDD) of Small-molecule Compounds and its Impact on Drug Development
10/03/2023 at 11:00 AM (EDT)  |  Recorded On: 10/03/2023
10/03/2023 at 11:00 AM (EDT)  |  Recorded On: 10/03/2023 Target-mediated drug disposition (TMDD) is a term to describe a nonlinear pharmacokinetics (PK) phenomenon that is caused by high-affinity binding of a compound to its pharmacologic targets. As the interaction between drug and its pharmacologic target belongs to the process of pharmacodynamics (PD), TMDD can be viewed as a consequence of "PD affecting PK". Both large-molecule and small-molecule compounds can undergo TMDD. However, TMDD in large-molecule compounds is well known due to its high prevalence, while TMDD in small molecule compounds is more counter-intuitive and has been an overlooked area. Recognizing TMDD in small-molecule compounds is important, as the information can be leveraged to select the appropriate dose regimen, improve clinical trial design, as well as predict pharmacological target occupancy. This webinar summarizes the general pharmacokinetic features that facilitate the recognition of small-molecule TMDD, provides case examples of different classes of small-molecules exhibiting TMDD, highlights the importance of recognizing TMDD of small-molecule compounds during clinical development, and presenting the pharmacometric models that have been used to facilitate the quantitative understanding of small molecules exhibiting TMDD.
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