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

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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. 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.

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.

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Authors and Affiliations

  1. Product Development, Actavis, 10065 Red Run Blvd, Owings Mills, Maryland, 21117, USA

    Yogeeta Narkar

  2. School of Pharmacy, University of Wisconsin-Madison, 777 Highland Ave., Madison, Wisconsin, 53705, USA

    Ronald Burnette, Ralph Albrecht & Joseph R. Robinson

  3. Animal Sciences, University of Wisconsin-Madison, 1675 Observatory Dr Madison, Wisconsin, 53706, USA

    Reiner Bleher, Ralph Albrecht & Angki Kandela

  4. Pediatrics, University of Wisconsin-Madison, 600 Highland Ave., Madison, Wisconsin, 53705, USA

    Ralph Albrecht

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  1. Yogeeta Narkar
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  2. Ronald Burnette
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  3. Reiner Bleher
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  4. Ralph Albrecht
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Correspondence to Yogeeta Narkar.

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Dr. Joseph R. Robinson has passed away.

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Appendix A

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Appendix B

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Figure 10

Plasma 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)

Figure 11A

Plasma 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)

Figure 11B

Plasma 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)

Table 5

Values of Ka (min−1) selected to fit oral absorption data in a step–function analysis (DOC 64 KB)

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Narkar, Y., Burnette, R., Bleher, R. et al. Evaluation of Mucosal Damage and Recovery in the Gastrointestinal Tract of Rats by a Penetration Enhancer. Pharm Res 25, 25–38 (2008). https://doi.org/10.1007/s11095-007-9509-8

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  • DOI: https://doi.org/10.1007/s11095-007-9509-8

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