Early ADME, PK/PD & Translational Modeling

Early ADME, PK/PD & Translational Modeling

Integrated Strategies for Drug Discovery and Development Success

---

Photo by Elimende Inagella on Unsplash

• Core Principles of Pharmacology (LADME)"},{text:
• In Vitro to In Vivo Extrapolation (IVIVE)"},{text:
• Microsomal Stability & Permeability Modeling"},{text:
• PK/PD Modeling Concepts"},{text:
• Early Safety Pharmacology & Regulatory Standards"}]},order_index:1,style:

---

Photo by Trnava University on Unsplash

1

Core Pharmacology Principles

Understanding LADME processes in drug discovery

---

Photo by Trnava University on Unsplash

• Pharmacokinetics (PK): What the body does to the drug vs. Pharmacodynamics (PD): What the drug does to the body
• PK follows LADME: Liberation (release from dosage form), Absorption (entry into bloodstream), Distribution (movement to tissues), Metabolism (chemical alteration), Excretion (elimination)
• AUC (Area Under the Curve) quantifies total drug exposure over time - critical for therapeutic efficacy and safety
• Early ADME assessment ensures appropriate exposure and reduces attrition rates
• Integrates drug design, medicinal chemistry, and molecular mechanism characterization

2

ADME & Translational Modeling

Predicting Human Outcomes from In Vitro Data

---

Photo by Deng Xiang on Unsplash

In Vitro Models

• Microsomal Stability: Assesses metabolic clearance rates using liver microsomes.
• Permeability (Caco-2/PAMPA): Predicts oral absorption potential based on intestinal barriers.

Translational Strategy (IVIVE)

• IVIVE (In Vitro-In Vivo Extrapolation) converts experimental clearance/permeability data to human PK predictions.
• Bridges bench-top data to patient physiology, reducing clinical risk.

3

PK/PD & Safety Pharmacology

Ensuring Efficacy and Therapeutic Index Safety

• PK/PD Modeling: Links drug concentration (PK) to effect magnitude (PD) using Emax and Sigmoid Emax models for exposure-response.
• Determines optimal dosing regimens and assesses time-course effect intensity throughout drug development.
• Safety Pharmacology (ICH S7A): Evaluates undesired effects on core systems (CNS, Cardiovascular, Respiratory). Required pre-Phase I.
• Secondary Organs: Gastrointestinal and Renal systems monitored for toxicological signals.
• Goal: Identify liabilities early to prevent clinical trial failures and optimize drug profiles.

Thank you for your attention. Any questions?

Integrated approaches are essential for clinical safety and success.

---

Photo by Jason Gooljar on Unsplash