Intestinal drug absorption kinetics determined in Ussing chambers is affected by the nature of the physiological media

Abstract

The aim of this study was to determine whether the nature of the physiological medium influences experimentally determined jejunal permeability. Acetaminophen (paracetamol) and vitamin C were used because their absorption pathways are well characterized. The study showed that the composition of the physiological solutions influenced (i) the conductance (G) of the intestinal mucosa and (ii) the intestinal permeation of acetaminophen and vitamin C. After 2 h, the transintestinal flux (Jms) of vitamin C was J=31.4 ± 1.44 µg.h⁻¹.cm⁻² with Ringer's solution, while with Sorensen's solution it was J=51.1 ± 7.09 µg.h⁻¹.cm⁻² and J=15.8 ± 1.92 µg.h⁻¹.cm⁻² with sodium-free Ringer's solution. The acetaminophen flux was J=17.9 ± 1.39 µg.h⁻¹.cm⁻² with Ringer's solution, while with Sorensen's solution it was J=12.6 ± 1.99 µg.h⁻¹.cm⁻². A strong correlation (R² = 0.979) was observed between conductance and vitamin C fluxes with different solutions, including Ringer’s, Sorensen’s, and sodium-free Ringer’s. For acetaminophen, the correlation was significant only with Ringer’s solution (R² = 0.976). The composition of the physiological solutions also influenced tissue responses to pharmacological effectors such as glucose and carbacholine. The proximal jejunum, when incubated in Ussing chambers, exhibited less morphological deterioration of epithelial villi. In conclusion, this study demonstrates that commonly used physiological media can affect the functional viability of intestinal tissue and influence experimental permeability data, highlighting the importance of carefully considering medium composition in in vitro intestinal drug absorption studies. Keywords: Intestinal absorption, physiological buffers composition, rat intestine, jejunum, physiological media, Ussing chambers, vitamin C, acetaminophen.