Developability assessment of clinical drug products with maximum absorbable doses
Xuan Ding1, John P Rose, Jan Van Gelder
1Pharmaceutical Sciences Research and Development, Eli Lilly and Company, Indianapolis, USA. ding xuan@lilly.com
International Journal of Pharmaceutics
|February 22, 2012
Summary
Maximum absorbable dose (D(abs)) quantifies oral drug absorption. Computer simulations offer more accurate D(abs) predictions than simple equations, aiding drug developability assessments.
Area of Science:
- Pharmacokinetics
- Drug Development
- Computational Modeling
Background:
- Maximum absorbable dose (D(abs)) is crucial for assessing oral drug absorption potential.
- Validating D(abs) calculation methods is essential for reliable drug developability assessments.
Purpose of the Study:
- To validate the use of D(abs) in drug developability assessments.
- To establish protocols and interpretation criteria for D(abs) application.
- To compare the predictive accuracy of different D(abs) calculation methods.
Main Methods:
- Calculated D(abs) using a simple equation and two simulation programs (GastroPlus, Eli Lilly program).
- Analyzed Phase I clinical trial data from dose escalation studies to determine clinical D(abs).
- Compared predicted D(abs) values with clinically observed absorption limits.
Main Results:
- All methods provided conservative D(abs) estimates compared to clinical data.
- Computer simulations (GastroPlus, Eli Lilly program) yielded more accurate D(abs) predictions.
- Simulations revealed complex absorption saturation behavior, often exceeding typical clinical doses.
Conclusions:
- Computer simulations are advantageous for drug developability assessment due to higher accuracy.
- Proposed an approach for absorption potential assessment based on validated D(abs) methods.
- Emphasized best practices for using D(abs) estimates in clinical formulation development.
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