Pharmaceutical Research

, Volume 25, Issue 1, pp 25–38 | Cite as

Evaluation of Mucosal Damage and Recovery in the Gastrointestinal Tract of Rats by a Penetration Enhancer

  • Yogeeta Narkar
  • Ronald Burnette
  • Reiner Bleher
  • Ralph Albrecht
  • Angki Kandela
  • Joseph R. Robinson
Research Paper

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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 words

absorption enhancement mucosal damage mucosal recovery oral absorption penetration enhancers 

Supplementary material

11095_2007_9509_MOESM1_ESM.doc (104 kb)
Appendix A(DOC 104 KB)
11095_2007_9509_MOESM2_ESM.doc (80 kb)
Appendix B(DOC 80 KB)
11095_2007_9509_MOESM3_ESM.ppt (34 kb)
Figure 10Plasma concentration-time profile of phenol red when orally administered with and without SDS (control, N = 12; SDS treatment, N = 6; each point represents mean ± SE. *p < 0.05, statistically significant difference from the control values) (PPT 34.5 KB)
11095_2007_9509_MOESM4_ESM.ppt (36 kb)
Figure 11APlasma concentration-time profile of phenol red. A after different recovery periods upon administration of 1% SDS (control and 1% SDS–1 h recovery, N = 12; SDS treatment, N = 6; each point represents mean ± SE. *p < 0.05, statistically significant difference from the control values) (PPT 35.5 KB)
11095_2007_9509_MOESM5_ESM.ppt (34 kb)
Figure 11BPlasma concentration-time profile of phenol red. B after 3-h recovery periods upon oral administration of SDS (control and 1% SDS–1 h recovery, N = 12; SDS treatment, N = 6; each point represents mean ± SE. *p < 0.05, statistically significant difference from the control values) (PPT 33.5 KB)
11095_2007_9509_MOESM6_ESM.doc (64 kb)
Table 5Values of Ka (min−1) selected to fit oral absorption data in a step–function analysis (DOC 64 KB)

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Yogeeta Narkar
    • 1
  • Ronald Burnette
    • 2
  • Reiner Bleher
    • 3
  • Ralph Albrecht
    • 2
    • 3
    • 4
  • Angki Kandela
    • 3
  • Joseph R. Robinson
    • 2
  1. 1.Product DevelopmentActavisOwings MillsUSA
  2. 2.School of PharmacyUniversity of Wisconsin-MadisonMadisonUSA
  3. 3.Animal SciencesUniversity of Wisconsin-MadisonWisconsinUSA
  4. 4.PediatricsUniversity of Wisconsin-MadisonMadisonUSA

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