Evaluation of Mucosal Damage and Recovery in the Gastrointestinal Tract of Rats by a Penetration Enhancer
- Yogeeta NarkarAffiliated withProduct Development, Actavis Email author
- , Ronald BurnetteAffiliated withSchool of Pharmacy, University of Wisconsin-Madison
- , Reiner BleherAffiliated withAnimal Sciences, University of Wisconsin-Madison
- , Ralph AlbrechtAffiliated withSchool of Pharmacy, University of Wisconsin-MadisonAnimal Sciences, University of Wisconsin-MadisonPediatrics, University of Wisconsin-Madison
- , Angki KandelaAffiliated withAnimal Sciences, University of Wisconsin-Madison
- , Joseph R. RobinsonAffiliated withSchool of Pharmacy, University of Wisconsin-Madison
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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. C max, AUC and K a decreased and T max 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.
Key wordsabsorption enhancement mucosal damage mucosal recovery oral absorption penetration enhancers
- Evaluation of Mucosal Damage and Recovery in the Gastrointestinal Tract of Rats by a Penetration Enhancer
Volume 25, Issue 1 , pp 25-38
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- Springer US
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- absorption enhancement
- mucosal damage
- mucosal recovery
- oral absorption
- penetration enhancers
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- Author Affiliations
- 1. Product Development, Actavis, 10065 Red Run Blvd, Owings Mills, Maryland, 21117, USA
- 2. School of Pharmacy, University of Wisconsin-Madison, 777 Highland Ave., Madison, Wisconsin, 53705, USA
- 3. Animal Sciences, University of Wisconsin-Madison, 1675 Observatory Dr Madison, Wisconsin, 53706, USA
- 4. Pediatrics, University of Wisconsin-Madison, 600 Highland Ave., Madison, Wisconsin, 53705, USA