Pharmacokinetics/pharmacodynamics model-supported early drug development.

Area of Science:

• Pharmacology
• Drug Development
• Quantitative Pharmacology

Background:

• Pharmacokinetic/pharmacodynamic (PK/PD) modeling and simulation (M&S) is vital for assessing dose-exposure-response relationships.
• Its application is well-established in late-stage drug development and regulatory decision-making.
• However, the significance of PK/PD M&S in preclinical and early clinical phases is often underestimated.

Purpose of the Study:

• To highlight the importance of PK/PD M&S in early drug development phases.
• To review literature demonstrating M&S applications for lead candidate optimization and dose projection.
• To provide expert insights into the practical utility of PK/PD model-based approaches for early decision-making.

Main Methods:

• Literature review of selected PK/PD M&S studies.
• Focus on M&S applications in lead candidate selection and optimization.
• Examination of preclinical PK/PD data for projecting clinical doses.
• Review of other M&S approaches like PBPK, meta-analysis, and PK-pharmacogenomics.

Main Results:

• M&S aids in selecting and optimizing lead drug candidates.
• Preclinical PK/PD data can effectively project the range of clinical doses.
• Comprehensive models forecast response probability using Phase 1 data.
• Various M&S techniques support early-stage drug development decisions.

Conclusions:

• PK/PD M&S significantly impacts early drug development decision-making.
• Model-based approaches improve the success rate from early to late stages.
• Embracing PK/PD M&S in early phases is essential for efficient drug development.