Al-Salami Hani, Butt Grant, Fawcett J Paul, Tucker Ian G, Golocorbin-Kon Svetlana, Mikov Momir
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Eur J Drug Metab Pharmacokinet. 2008 Apr-Jun;33(2):101-6. doi: 10.1007/BF03191026.
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.
格列齐特是一种对糖尿病具有有益胰外作用的磺脲类药物,给予益生菌可能会增强其作用。本研究的目的是调查益生菌对格列齐特药代动力学的影响,以及益生菌和格列齐特对健康大鼠和糖尿病大鼠血糖水平的作用。将雄性Wistar大鼠(2至3个月,体重350±50 g)随机分为4组(n = 10),其中两组经静脉注射30 mg/kg四氧嘧啶诱导糖尿病。然后,一组健康大鼠和一组糖尿病大鼠用益生菌(75 mg/kg)灌胃三天,之后对所有组经口灌胃给予格列齐特混悬液(20 mg/kg)。给药后10小时内的不同时间点从尾静脉采集血样,用于测定血糖和格列齐特血清浓度。结果发现,益生菌治疗对健康大鼠的血糖水平没有影响,但在糖尿病大鼠中降低了血糖水平(高达2倍;p < 0.01)。益生菌治疗降低了健康大鼠中格列齐特的生物利用度(3倍),而在糖尿病大鼠中提高了格列齐特的生物利用度(2倍;p < 0.01)。尽管格列齐特的生物利用度发生了变化,但它对健康大鼠或糖尿病大鼠的血糖水平均无影响。总之,糖尿病大鼠的益生菌治疗通过非胰岛素依赖机制提高了格列齐特的生物利用度并降低了血糖水平,这表明给予益生菌作为糖尿病治疗的辅助疗法可能有益。