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The influence of 3α,7α-dihydroxy-12-keto-5β-cholanate on gliclazide pharmacokinetics and glucose levels in a rat model of diabetes

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Summary

The aim of this study was to investigate the pharmacokinetics and glucose-lowering activity of gliclazide alone and in combination with the bile acid salt, sodium 3α,7α-dihydroxy-12-keto-5β-cholanate (MKC), in a rat model of type I diabetes. Eighty male Wistar rats were divided into eight groups (n=10). Four groups were treated with alloxan (30 mg/kg) to induce diabetes. One group of healthy and one group of diabetic rats were administered gliclazide (20 mg/kg), MKC (4 mg/kg) or a combination of gliclazide (20 mg/kg) and MKC (4 mg/kg). One group of healthy and one group of diabetic rats were used as controls. Blood samples were collected from the tail vein 6 hours post-dose and the plasma was analyzed for glucose concentrations. It was found that gliclazide bioavailability was increased in healthy rats when coadministered with MKC, but there was no difference in glucose levels. Gliclazide bioavailability was much lower in diabetic rats and was not altered by MKC. However, the hypoglycemic effect of the combination of gliclazide and MKC was significantly greater in diabetic rats than that of gliclazide alone. It was demonstrated that the combination of MKC and gliclazide produced a significant hypoglycemic effect in a rat model of Type I diabetes. As gliclazide alone does not have a hypoglycemic effect on Type 1 diabetic rats, it can be concluded that gliclazide potentiates hypoglycemic effect of MKC in Type 1 diabetic rats.

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Authors and Affiliations

  1. School of Pharmacy, University of Otago, Dunedin, New Zealand

    Momir Mikov, Hani Al-Salami & J. Paul Fawcett

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

    Svetlana Golocorbin-Kon & Aleksandar Raskovic

  3. Department of Pharmacology, Medical Faculty, Banja Luka, Bosnia and Herzegovina

    Ranko Skrbic

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  1. Momir Mikov
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  2. Hani Al-Salami
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  3. Svetlana Golocorbin-Kon
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  5. Aleksandar Raskovic
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  6. J. Paul Fawcett
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Correspondence to Momir Mikov.

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Mikov, M., Al-Salami, H., Golocorbin-Kon, S. et al. The influence of 3α,7α-dihydroxy-12-keto-5β-cholanate on gliclazide pharmacokinetics and glucose levels in a rat model of diabetes. Eur. J. Drug Metabol. Pharmacokinet. 33, 137–142 (2008). https://doi.org/10.1007/BF03191110

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  • DOI: https://doi.org/10.1007/BF03191110

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