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  • Identification of solubility-limited absorption of oral anticancer drugs using PBPK modeling based on rat PK and its relevance to human.

Identification of solubility-limited absorption of oral anticancer drugs using PBPK modeling based on rat PK and its relevance to human.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (2020-06-21)
Christina Fink, Marc Lecomte, Lassina Badolo, Knut Wagner, Karsten Mäder, Sheila-Annie Peters
ANOTACE

Solubility is one of the key parameters that is optimized during drug discovery to ensure sufficient drug concentration in systemic circulation and to achieve the desired pharmacological response. We recently reported the application of PBPK analysis of early clinical pharmacokinetic data to identify drugs whose absorption are truly limited by solubility. In this work, we selected ten anticancer drugs that exhibit poor in vitro solubility to explore the utility of this approach to identify solubility-limited absorption based on rat pharmacokinetic data and compare the findings to human data. Oral rat pharmacokinetic studies were performed at the body weight-scaled doses of the model drugs' human food effect studies, and analyzed using a top-down PBPK modeling approach. A good correlation of solubility-limited absorption in rat and human was observed. These results allow an early identification of drugs with truly solubility-limited absorption, with the potential to guide decisions and save valuable resources in drug development.

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Sigma-Aldrich
Butyl methyl ether, 99%
Sigma-Aldrich
Imatinib