Evaluation of Mucosal Damage and Recovery in the Gastrointestinal Tract of Rats by a Penetration Enhancer
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- Narkar, Y., Burnette, R., Bleher, R. et al. Pharm Res (2008) 25: 25. doi:10.1007/s11095-007-9509-8
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To evaluate absorption barrier recovery in the gastrointestinal tract after treatment with a penetration enhancer by using a poorly absorbed marker and correlate results with morphological recovery.
Oral gavage of sodium dodecyl sulfate (SDS) was given to Wistar rats. Phenol red (PR) was given at different time points following administration of SDS. Blood samples were obtained from the jugular vein. Pharmacokinetic analysis was performed on the in vivo data using WinNonlin and MATLAB®5 software. The pharmacokinetic parameters of PR were compared to the negative control to measure functional recovery. The intestinal tissues were observed using light and transmission electron microscopy.
Absorption was highest when PR was co-administered with SDS. Cmax, AUC and Ka decreased and Tmax and MAT increased as the recovery period (time between administration of SDS and PR) increased. The pharmacokinetic parameters approached the negative control profile in one hour after treatment with 1% SDS. Microscopy results showed recovery of paracellular and transcellular barrier at this time.
Absorption barrier recovery could be measured using a poorly absorbed marker. Functional recovery showed a good correlation with morphological recovery. The local effects of SDS were found to be temporary and reversible.