Polar interactions drug/phospholipids estimated by IAM-HPLC vs cultured cell line passage data: Their relationships and comparison of their effectiveness in predicting drug human intestinal absorption

International Journal of Pharmaceutics
Lucia GrumettoF Barbato

Abstract

The relationships between data of passage through Caco-2 cultured cell lines (log Papp), taken from the literature, for 38 structurally unrelated compounds and both n-octanol lipophilicity parameters (log P(N) and log D(7.4)) and phospholipid affinity indexes were investigated. Phospholipid affinity(log k W(IAM)) was experimentally determined by HPLC on two different phospholipid stationary phases and the polar/electrostatic interaction component drug/phospholipids (Δ log k W(IAM)) was calculated according to a method we previously proposed. Log Papp moderately related to lipophilicity values measured at pH 7.4 (log D(7.4)), according to a parabolic pattern, but poorly related with log k W(IAM). Furthermore, a significant inverse linear relationship with Δ l og k W(IAM) values was only observed for the analytes with m.w. >300 Da, for which paracellular diffusion can be considered a minor transport route in vivo. Indeed, it has been reported that Caco-2 passage data also encode secondary passage mechanisms, which participate in a different extent to the jejunal absorption in vivo and cannot be directly equated to the corresponding human in situ log Peff values, unless a normalization is performed. In an attempt to elucidate this...Continue Reading

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Citations

Jun 24, 2017·Expert Opinion on Drug Discovery·Fotios TsopelasAnna Tsantili-Kakoulidou
Feb 24, 2020·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Giuseppe ErmondiGiulia Caron
Aug 18, 2020·Journal of Chemical Information and Modeling·Xiting WangTao Lu

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