Indirect Modeling of Post-Prandial Intestinal Lymphatic Uptake of Halofantrine Using PBPK Approaches: Limitations and Implications.

ABSTRACT: Background/Objectives: Despite the recognized importance and distinctive characteristics of the intestinal lymphatic pathway in drug absorption, its pharmacokinetic modeling remains largely unexplored. This study aimed to address this gap by developing a physiologically based pharmacokinetic model (PBPK) to represent the oral lymphatic uptake of halofantrine following a fatty meal. Methods: Using GastroPlus™ 9.8.3 and published literature data, halofantrine absorption, distribution, metabolism, and elimination in both fasting and fed states were modeled. As the used software does not directly simulate intestinal lymphatic transport, lymphatic involvement in the fed state was examined indirectly through parameter adjustments such as first-pass metabolism, pKa-driven solubility

SUBMITTER: Yousef M 

PROVIDER: S-EPMC12473779 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature