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Gliclazide reduces MKC intestinal transport in healthy but not diabetic rats

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Summary

The aim is to investigate the influence of the antidiabetic drug gliclazide on the ileal permeation of the semisynthetic bile acid, MKC, in tissues from healthy and diabetic rats. Sixteen Wistar rats (350±50 g) were randomly allocated into four groups (4 rats per group, 8 chambers per rat i.e. n=32) two of which were made diabetic (given alloxan i.v.30 mg/kg). Group 1 was used to measure the permeation of MKC (50 μg/ml) alone (control) while group 2 to measure MKC permeation in the presence of gliclazide (200μg/ml). The diabetic groups 3 (gliclazide) and 4 (MKC+gliclazide) were treated in the same way. Rats were sacrificed and tissues were mounted into the Ussing chamber for the measurement of MKC mucosal to serosal (absorptive) and serosal to mucosal (secretory) fluxes. In healthy tissues, gliclazide reduced MKC absorptive flux (p<0.01) and increased its secretory flux (p<0.01). In diabetic tissues, gliclazide had no effect on either the absorptive or the secretory fluxes of MKC. The lack of effect of gliclazide on MKC permeation in diabetic tissues suggests the absence or suppressed drug transporters. Furthermore, gliclazide inhibition of MKC absorptive flux and induction of MKC secretory flux in healthy tissues may result from the selective inhibition of an efflux drug transporter.

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Authors and Affiliations

  1. School of Pharmacy, University of Otago, POBox 913, 9054, Dunedin, New Zealand

    Hani Al-Salami, Ian Tucker, Paul J Fawcett & Momir Mikov

  2. Department of Physiology, University of Otago, Dunedin, New Zealand

    Grant Butt

  3. Department of Pharmacy, Medical Faculty Novi Sad, Novi Sad, Serbia

    Svetlana Golo-Corbin-Kon

  4. Department of Pharmacology and Toxicology, Medical Faculty Novi Sad, Novi Sad, Serbia

    Ivan Mikov

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Al-Salami, H., Butt, G., Tucker, I. et al. Gliclazide reduces MKC intestinal transport in healthy but not diabetic rats. Eur. J. Drug Metabol. Pharmacokinet. 34, 43–50 (2009). https://doi.org/10.1007/BF03191383

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