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Войти в исследования Pharmaceutical research · 2026
Estimating Human Jejunal Effective Permeability Using Numerical Deconvolution of Oral Solution Concentration Data.
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Zhang Wenqian, Geng Jia, He Xingrui, Yi Hanxi, Dong Jie, Mei Lin, Xie Feifan
Аннотация
AIMS: Accurate determination of human intestinal effective permeability (Peff) typically relies on technically challenging human intestinal perfusion experiments. This study aimed to develop a numerical deconvolution method to estimate jejunal permeability using concentration data obtained from oral solution and intravenous administration.
METHODS: Twenty-seven drugs (4 acidic, 11 basic, 7 amphophilic, and 5 neutral) were included using predefined criteria. Numerical deconvolution of intravenous and oral solution data across five time windows (0.25-0.75, 0.5-1, 0.75-1.25, 1-1.5, and 1.5-2 h) was applied to estimate regional jejunal permeability. Estimates were generated under two conditions: uncorrected (Peff, uncorr) and corrected for first-pass metabolism (Peff, FP_corr). The resulting permeability values were compared with observed human perfusion data (Peff, obs), as well as with the reported three-parameter average model and the site-specific data-based deconvolution method.
RESULTS: Correlations of jejunal permeability were performed for 26 drugs (lisinopril excluded due to unreliable Peff, obs). The 0.25-0.75 h window showed the best agreement with observed values. Within this window, correlations with Peff, obs were moderate for Peff, uncorr (R2 = 0.47) and strong for Peff, FP_corr (R2 = 0.83). The proposed method outperformed the three-parameter average model (R2: 0.83 vs 0.57) and was comparable to the site-specific deconvolution method (R2: 0.94 vs 0.96) using overlapping compounds.
CONCLUSIONS: Our oral solution-based numerical deconvolution method, accounting for first-pass metabolism, enables accurate estimation of jejunal permeability.
METHODS: Twenty-seven drugs (4 acidic, 11 basic, 7 amphophilic, and 5 neutral) were included using predefined criteria. Numerical deconvolution of intravenous and oral solution data across five time windows (0.25-0.75, 0.5-1, 0.75-1.25, 1-1.5, and 1.5-2 h) was applied to estimate regional jejunal permeability. Estimates were generated under two conditions: uncorrected (Peff, uncorr) and corrected for first-pass metabolism (Peff, FP_corr). The resulting permeability values were compared with observed human perfusion data (Peff, obs), as well as with the reported three-parameter average model and the site-specific data-based deconvolution method.
RESULTS: Correlations of jejunal permeability were performed for 26 drugs (lisinopril excluded due to unreliable Peff, obs). The 0.25-0.75 h window showed the best agreement with observed values. Within this window, correlations with Peff, obs were moderate for Peff, uncorr (R2 = 0.47) and strong for Peff, FP_corr (R2 = 0.83). The proposed method outperformed the three-parameter average model (R2: 0.83 vs 0.57) and was comparable to the site-specific deconvolution method (R2: 0.94 vs 0.96) using overlapping compounds.
CONCLUSIONS: Our oral solution-based numerical deconvolution method, accounting for first-pass metabolism, enables accurate estimation of jejunal permeability.