Comparision of the phenol red, gravimetric, and synthesized mPEG-PR methods for correcting water flux using the single-pass intestinal perfusion method.

Phenol red and PEG-4000, the usual non-absorbable indicators, have non-negligible absorption problems in measuring water flux. mPEG-PR, combined phenol red with mPEG-4000, was first synthesized and could decrease absorption. However, its application has not been confirmed. The purpose of this study was to explore the applicability of mPEG-PR as a novel non-absorption indicator in the in situ single-pass intestinal perfusion (SPIP) experiment. Six model drugs (atenolol ranitidine, ibuprofen, ketoprofen, antipyrine, hydrochlorothiazide) were used to compare the accuracy of four measuring methods including phenol red, mPEG-PR, gravimetric, and non-corrected methods of correcting intestinal fluid transport. Moreover, we evaluated the correlations between the effective permeability coefficients (P) in rat and fraction dose absorbed (F) in human, P in human, and apparent permeability coefficients (P) by the Ussing Chamber system using human tissue. Among these methods, mPEG-PR was the most reliable approach, which avoided the absorption of phenol red method and mucous shedding or water evaporation of gravimetric method. An excellent correlation was obtained between the P of rat and F of human. Our results of this study indicated that mPEG-PR was a stable and accurate non-absorbable indicator to correct water flux in the in situ SPIP model, which could be developed to predict the human F.