Summary
The action of gliclazide, a sulphonylurea with beneficial extrapancreatic effects in diabetes, may be enhanced by administering probiotics. The aim of this study was to investigate the influence of probiotics on gliclazide pharmacokinetics and the effect of both probiotics and gliclazide on blood glucose levels in healthy and diabetic rats. Male Wistar rats (2 to 3 months, weight 350 ± 50 g) were randomly allocated to 4 groups (n =10), two of which were treated with alloxan i.v. 30 mg/kg to induce diabetes. One group of healthy and one group of diabetic rats were then gavaged with probiotics (75 mg/kg) for three days after which a gliclazide suspension (20 mg/kg) was administered by gavage to all groups. Blood samples were collected from the tail vein at various time points for 10 hours post-administration for the determination of blood glucose and gliclazide serum concentrations. It was found that probiotic treatment had no effect on blood glucose levels in healthy rats, but it reduced them (up to 2-fold;p < 0.01) in diabetic rats. Probiotic treatment reduced gliclazide bioavailability in healthy rats (3-fold) whereas it increased gliclazide bioavailability in diabetic rats (2-fold;p < 0.01). Gliclazide had no effect on blood glucose levels in either healthy or diabetic rats despite the changes in its bioavailability. In conclusion, the probiotic treatment of diabetic rats increases gliclazide bioavailability and lowers blood glucose levels by insulin-independent mechanisms, suggesting that the administration of probiotics may be beneficial as adjunct therapy in the treatment of diabetes.
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References
FAOA/WHO. (2002): Guidelines for the Evaluation of Probiotics in Food. Report on drafting guidelines for the evaluation of probiotics in food. Ontario, Canada.
Bezkorovainy A. (2001): Probiotics: determinants of survival and growth in the gut. Am. J. Clin. Nutr., Suppl (2), 399–405.
Karimi O., Pena A. (2003): Probiotics: Isolated bacteria strain or mixtures of different strains? Two different approaches in the use of probiotics as therapeutics. Drugs Today, 39, 565–597.
Billoo A., Memon M., Khaskheli S.A., Murtaza G., Iqbal K., Saeed Shekhani M., et al (2003): Role of a probiotic (Saccharomyces boulardii) in management and prevention of diarrhoea. World. J. Gastroenterol., 6, 4557–4560.
Mikov M. (1994): The metabolism of drugs by the gut flora. Eur. J. Drug. Metab. Pharmacokinet., 19, 201–207.
Ghosh S., van Heel D., Playford R.J. (2004): Probiotics in inflammatory bowel disease: is it all gut flora modulation? Gut, 53, 620–622.
Schultz M., Linde H.J., Lehn N., Zimmermann K., Grossmann J., Falk W., et al. (2003): Immunomodulatory consequences of oral administration ofLactobacillus rhamnosus strain GG in healthy volunteers. J. Dairy. Res., 70, 165–173.
Gill H.S., Rutherfurd K.J., Prasad J., Gopal P.K. (2000): Enhancement of natural and acquired immunity byLactobacillus rhamnosus (HN001),Lactobacillus acidophilus (HN017) andBifidobacterium lactis (HN019). Br. J. Nutr., 83, 167–176.
Onkamo P., Vaananen S., Karvonen M., Tuomilehto J. (1999): Worldwide increase in incidence of type I diabetes— the analysis of the data on published incidence trends. Diabetologia, 42, 1395–1403.
Pundziute-Lycka A., Dahlquist G., Nystrom L, Arnqvist H., Bjork E., Blohme G., et al. (2002): The incidence of Type I diabetes has not increased but shifted to a younger age at diagnosis in the 0–34 years group in Sweden 1983–1998. Diabetologia, 45, 783–791.
Libman I., Songer T., LaPorte R. (1993): How many people in the U.S. have IDDM?. Diabetes Care, 16, 841–852.
Bourlioux P., Koletzko B., Guarner F., Braesco V. (2003): The intestine and its microflora are partners for the protection of the host. Am. J. Clin. Nutr., 78, 675–683.
Calcinaro F., Dionisi S., Marinaro M., Candeloro P., Bonato V., Marzotti S., et al. (2005): Oral probiotic administration induces interleukin-10 production and prevents spontaneous autoimmune diabetes in the non-obese diabetic mouse. Diabetologia, 48, 1565–1575.
Rendali M. (2004): The role of sulphonylureas in the management of type 2 Diabetes Mellitus. Drugs, 64, 1349–1358.
Yaris F., Yaris E., Kadioglu M., Ulku C, Kesim M., Kalyoncu N.I. (2004): Normal pregnancy outcome following inadvertent exposure to rosiglitazone, gliclazide, and atorvastatin in a diabetic and hypertensive woman. Reprod. Toxicol., 18, 619–621.
Campbell D.B., Lavielle R., Nathan C. (1991): The mode of action and clinical pharmacology of gliclazide: a review. Diabetes. Res. Clin. Pract., 14, Suppl 2, 21–36.
Smith R.J. (1990): Effects of the sulfonylureas on muscle glucose homeostasis. Am. J. Med., 89, 38S-43S.
Renier G., Desfaits A.C., Serri O. (2000): Effect of gliclazide on monocyte-endothelium interactions in diabetes. J. Diabetes Complications, 14, 215–223.
Palmer K.J., Brogden R.N. (1993): Gliclazide. An update of its pharmacological properties and therapeutic efficacy in non-insulin-dependent diabetes mellitus. Drugs, 46, 92–125.
Al-Salami H., Butt G., Tucker I., Mikov M. (2008): Influence of the semisynthetic bile acid MKC on the ileal permeation of gliclazidein vitro in healthy and diabetic rats treated with probiotics. Methods. Find. Exp. Clin. Pharmacol., 30, 1–7.
Carvalhol E., Carvalhol S., Ferreira. L.M. (2003): Experimental model of induction of diabetes mellitus in rats. Acta Cirurg. Bras., 18, 120–167.
Korec R. (1980): Treatment of alloxan and streptozotocin diabetes in rats by intrafamiliar homo (allo) transplantation of neonatal pancreases. Endocrinol. Exp., 14, 191–198.
Stetinova V., Kvetina J., Pastera J., Polaskova A., Prazakova M. (2007): Gliclazide: pharmacokinetic-pharmacodynamic relationships in rats. Biopharm. Drug Dispos., 28, 241–248.
Bachmann K., Pardoe D., White D. (1996): Scaling basic toxicokinetic parameters from rat to man. Environ. Health. Perspect., 104, 400–407.
Alam M.J., Rahman M.A. (1971): Changes in the saccharoid fraction in rats with alloxan-induced diabetes or injected with epinephrine. Clin. Chem., 17, 915–920.
Khavinson V.K. (2005): Effect of tetrapeptide on insulin biosynthesis in rats with alloxan-induced diabetes. Bull. Exp. Biol. Med., 140, 452–454.
Park J.Y., Kim K.A., Park P.W., Park C.W., Shin J.G. (2003): Effect of rifampin on the pharmacokinetics and pharmacodynamics of gliclazide. Clin. Pharmacol. Ther., 74, 334–340.
Rouini M.R., Mohajer A., Tahami M.H. (2003): A simple and sensitive HPLC method for determination of gliclazide in human serum. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sei., 785, 383–386.
Drucker D.J. (2001): Minireview: the glucagon-like peptides. Endocrinology, 142, 521–527.
Drucker D.J. (2007): The role of gut hormones in glucose homeostasis. J. Clin. Invest., 117, 24–32.
Bansil R., Stanley E., LaMont J.T. (1995): Mucin biophysics. Annu. Rev. Physiol. 57, 635–657.
Ceriello A. (2006): Effects of gliclazide beyond metabolic control. Metabolism 55, Suppl 1, S5–10.
Da Tos V., Maran A., Vigili De Kreutzenberg. Marchetto S., Tadiotto F., Bettio M. (2000): Mechanisms of acute and chronic hypoglycemic action of gliclazide. Acta. Diabetol. 37, 201–206.
Delrat P., Paraire M., Jochemsen R. (2002): Complete bioavailability and lack of food-effect on pharmacokinetics of gliclazide 30 mg modified release in healthy volunteers. Biopharm. Drug. Dispos., 23, 151–157.
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Al-Salami, H., Butt, G., Fawcett, J.P. et al. Probiotic treatment reduces blood glucose levels and increases systemic absorption of gliclazide in diabetic rats. Eur. J. Drug Metabol. Pharmacokinet. 33, 101–106 (2008). https://doi.org/10.1007/BF03191026
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DOI: https://doi.org/10.1007/BF03191026