EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS 2008, Vol. 33, No.2, pp. 101-106 Pro biotic treatment reduces blood glucose levels and increases systemic absorption of gliclazide in diabetic rats HANI AL-SALAMI l , GRANT BUTT 2 , J PAUL FAWCETT l , IAN G TUCKER l , SYETLANA GOLOCORBIN-KON 3 , MOMIR MIKOy l I School of Pharmacy, University of Otago, Dunedin, New Zealand 2 Department of Physiology, University of Otago, Dunedin, New Zealand 3 Department of Pharmacy, Medical Faculty, Novi Sad, Republic of Serbia Received for publication: December 6,2007 Key words: Diabetes, probiotics, gliclazide, pharmacokinetics, blood glucose 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 mglkg to induce diabetes. One group of healthy and one group of diabetic rats were then gavaged with probiotics (75 mglkg) 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. 'INTRODUCTION Probiotics are dietary supplements containing live bacteria which, when administered in adequate amounts, confer a health benefit on the host (1). Combinations of different bacterial strains can be used (2,3) but Lactobacillus and Bifidobacteria are 'Please send reprint request to: Prof. Momir Mikov, momir.mikov@stonebow.otago.ac.nz common choices (3). Probiotics have been shown to have positive therapeutic effects in a wide range of conditions including infections, allergies, and meta- bolic disorders such as diabetes (4-6). It has been suggested that their efficacy is probably the result of their ability to stimulate the immune system (7,8). Type 1 diabetes (TlD) is a metabolic disorder char- acterized by the destruction of the pancreatic ｾＭｩｳｬ･ｴ cells, leading to the complete loss of insulin produc- tion. The incidence of Tl 0 in children is increasing in many countries (9), and it now appears to be more