Complete bioavailability and lack of food-effect on pharmacokinetics of gliclazide 30 mg modified release in healthy volunteers

A new modified release (MR) formulation containing 30 mg of gliclazide was developed to obtain a better predictable release of the active principle and to allow once-daily dosing regimen. An absolute bioavailability study was carried out to characterise the performance of the new formulation and the food-effect was also investigated in a separate study. Both studies were single dose, randomised, open label, two way cross over studies with a wash out period between doses. For the bioavailability study, each volunteer received 30 mg of gliclazide given either as a 1 h intravenous infusion or as a 30 mg MR tablet. For the food-effect study, the treatment was given either fasted or 10 min after the start of a standardised Melander breakfast. Blood samples were collected up to 72 h after administrations and plasma samples assayed for gliclazide concentrations using a reverse-phase HPLC method with UV detection. Mean absolute bioavailability of gliclazide was 97% and ranged between 79 and 110% showing complete absorption. A similar moderate to low variability was observed after IV and oral administration showing the MR formulation did not add to the overall variability which is solely due to the disposition parameters, in particular metabolism of gliclazide. No significant difference was observed in t(max), t(1/2z), C(max) and AUC of gliclazide after administration of the 30 mg MR tablet under fasted and fed conditions. In conclusion, after single oral administration of a 30 mg MR tablet, gliclazide was completely absorbed both under fasted and fed conditions. A consistent and optimal release of gliclazide from this formulation leads to a low to moderate overall variability of its pharmacokinetic parameters. Diamicron 30 mg MR can be given without regards to meals i.e. before, during or after breakfast.     

Gliclazide: pharmacokinetic-pharmacodynamic relationships in rats

The relationship between the pharmacokinetics of gliclazide and its antidiabetic efficacy were evaluated on the basis of experimental determination of changes with time in the plasma levels of this antidiabetic agent and those of glucose. The experiment included rats with both initial normal glycaemia and alloxan-induced hyperglycaemia (glycaemia increased by a minimum of 30%). Pharmacokinetic and pharmacodynamic parameters were examined in the interval of 30 to 180 min after p.o. administration of a single dose of 25 mg/kg of gliclazide. The drug was administered on day 4, following a single i.v. dose of either 50 mg/kg of alloxan (hyperglycaemic group) or the injection vehicle (control group). Even though the biological availability of gliclazide was similar in both normoglycaemic and hyperglycaemic animals, the gliclazide-induced hypoglycaemizing response was not uniform: until 60 min, the decrease of glycaemia was smaller in animals with alloxan hyperglycaemia (23% decrease at 60 min) in contrast to the normoglycaemic animals (36% decrease at 60 min), at later times, the intensity of this hypoglycaemizing effect of gliclazide persisted in the hyperglycaemic animals, while in the normoglycaemic ones, a reversal of the hypoglycaemizing effect occurred.     

Influence of the semisynthetic bile acid MKC on the ileal permeation of gliclazide in vitro in healthy and diabetic rats treated with probiotics

The aim of this study was to investigate the influence of sodium 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate (MKC) on the ileal permeation of gliclazide in healthy and diabetic rats treated with probiotics. Male Wistar rats (2-3 months, 350 +/- 50 g) were randomly allocated into four groups (n = 32); Groups 1 and 2 were healthy controls and Groups 3 and 4 were diabetic rats (alloxan 30 mg/kg was administered i.v.), which were administered probiotics for three days after the rats became diabetics. The rats were sacrificed and tissues were mounted on Ussing chambers. Then, gliclazide (200 microg/ml) was added to all the groups, while MKC (50 microg/ml) was given to Groups 2 and 4, for the measurement of the mucosal to serosal absorption Jss(MtoS) and serosal to mucosal secretion Jss(StoM) of gliclazide. In the tissues of healthy rats treated with probiotics, MKC stimulated the net absorption of gliclazide by stimulating the absorptive and reducing the secretory unidirectional fluxes, while in tissues from diabetic rats treated with probiotics, MKC had no effect. In healthy rats treated with probiotics, the degradation of MKC by bacterial polypeptides produced divalent bile salts that inhibited Mrp2, which resulted in reducing secretion and stimulating the absorption of gliclazide. In contrast, in diabetic rats treated with probiotics, MKC had no effect possibly due to a difference in the metabolic profile and resulting in no net flux.     

Gliclazide modified release

Gliclazide modified release (MR) is a new formulation of the drug gliclazide and is given once daily. The hydrophilic matrix of hypromellose-based polymer in the new formulation effects a progressive release of the drug which parallels the 24-hour glycaemic profile in untreated patients with type 2 diabetes mellitus. The formulation shows high bioavailability and its absorption profile is unaffected by coadministration with food. Mean plasma glucose levels are significantly reduced over a 24-hour period in patients with type 2 diabetes mellitus treated with gliclazide MR once daily, in both fasting and postprandial states. No cardiovascular ATP-sensitive potassium channel interaction has been observed at therapeutic concentrations of gliclazide MR. Gliclazide MR has also demonstrated antioxidant properties that are independent of glycaemic control. In a randomised, double-blind, multicentre study, gliclazide MR 30 to 120 mg once daily showed similar efficacy to gliclazide immediate release (IR) 80 to 320 mg/day (in divided doses for doses >80 mg) in patients with type 2 diabetes mellitus over a 10-month period, reducing glycosylated haemoglobin (HbA(1c)) and fasting plasma glucose (FPG) to a similar extent. The drug appeared most efficacious in patients who had previously been treated by diet alone, where significant reductions in HbA(1c) from baseline of 0.9% and 0.95% were seen at 10 and 24 months. Similarly, a sustained effect of gliclazide MR was observed in a subgroup of elderly patients defined a priori; HbA(1c) was decreased to a similar degree to that observed in the general study population. Gliclazide MR showed similar tolerability to gliclazide IR after 10 months' treatment in the randomised trial. The most commonly observed adverse events were arthralgia, arthritis, back pain and bronchitis (each <5%). Bodyweight remained stable. In this study no episodes of nocturnal hypoglycaemia or hypoglycaemia requiring third party assistance were observed during treatment with gliclazide MR. Episodes of symptomatic hypoglycaemia were infrequent, occurring in approximately 5% of patients.     

Influence of food intake on the absorption and effect of glipizide in diabetics and in healthy subjects

Summary The influence of a standardized breakfast on the single dose (5 mg) kinetics and effects of glipizide was examined in 9 healthy volunteers and in 14 diabetics not previously exposed to a sulfonylurea. In the volunteers, glipizide caused an increase in plasma insulin and a reduction in blood glucose both during continued fasting and when the drug was taken with the breakfast. Food intake did not influence the peak concentration, the elimination half-life or the bioavailability of the drug. However, food intake significantly delayed the absorption of glipizide by about 0.5 h. In the patients, glipizide produced a significant increase in plasma insulin and a significant diminution of the rise in blood glucose in response to the meal. Starting at breakfast and for 45 min thereafter serum glipizide concentrations were significantly higher when the drug was taken 0.5 h before the meal, than when ingested concurrently with it. With the former treatment, the increase in plasma insulin occurred earlier and the blood glucose reduction was pronouncedly greater than with the latter treatment. As the absorption of glipizide may be delayed by concurrent breakfast, this may help to explain, why the administration of glipizide 0.5 h before breakfast led to a more appropriate relation between the serum concentration of the drug and the metabolic impact of the meal, thereby promoting more appropriate insulin release and better glucose disposition than after concurrent intake of the drug and breakfast.     

Effect of middle-term gliclazide treatment on insulin secretion in non-insulin dependent diabetics

Summary

Insulin secretion was studied in 12 non-insulin dependent diabetics during middle-term administration of the sulphonylurea gliclazide. Blood sugar, C-peptide and glucagon were also estimated during the intravenous glucose tolerance and arginine tests performed before and after therapy. After 3 months of gliclazide/therapy (240?mg/day) in addition to a low carbohydrate diet, the intravenous glucose tolerance test showed a significant reduction in blood sugar levels and in the partial and total areas under the blood sugar curve, as well as an improvement in early insulin secretion, characterized by a significant increase in plasma C-peptide at 4, 10 and 20 minutes. Plasma glucagon levels were not affected by the sulphonylurea therapy. In the arginine test, blood sugar levels were lower at the end of the treatment period; plasma insulin, C-peptide and glucagon did not change significantly. In this study, plasma C-peptide has proved to be a better indicator of stimulated insulin secretion than plasma insulin levels. The scarcity of hypo-glycaemic episodes during therapy with gliclazide may be related to the selective stimulation of early insulin secretion by this drug.     

Changes in insulin secretion and calcium distribution within B cells induced by gliclazide

Using the pyroantimonate technique, the ultracytochemical distribution of calcium within B cells was studied in isolated rat pancreatic islets incubated during 5, 15 and 30 min with 8.3 mM glucose alone or together with 76 microgram glicazide. Glucose alone produced a continuous increment in the total number of calcium pyroantimonate precipitates (CPP) throughout the incubation period studied. The CPP were mainly associated to the cytoplasmic matrix and the secretory granules at 5 and 15 min and almost evenly distributed between these structures and the plasma membrane at 30 min. Gliclazide plus glucose produced a significant increment, above the glucose values, of the total CPP at 5 min and a later decrease of such values at 15 and 30 min. At 5 min, the incremented total CPP was mainly associated to the secretory granules and the cytoplasmic matrix. The increment in CPP preceded the largest effect of gliclazide on insulin secretion. The latter diminution of CPP induced by gliclazide could contribute to the failure of this drug, as well as other oral hypoglycemic agents, to elicit a second phase of insulin secretion. Changes induced by gliclazide upon B-cell CPP content and distribution might suggest that beyond the effective role of cytosolic calcium in the control of insulin secretion, the cation might reach a threshold concentration in some cell structures to assure the normal development of the secretory process.     

Gliclazide. A preliminary review of its pharmacodynamic properties and therapeutic efficacy in diabetes mellitus

Gliclazide is a 'second generation' oral hypoglycaemic agent. The particular interest with this drug is that it has shown certain effects on the blood for which it is hoped there may be some clinical benefit in diabetic angiopathies. Both in animal and human studies it has demonstrated a reduction in platelet adhesiveness and aggregation, whilst possible enhancement of platelet metabolism, reduction of coagulant factors, as well as increased fibrinolytic activity, are still being investigated. Initial trials have suggested that gliclazide therapy may reverse or at least slow down the progression of diabetic retinopathy. However, a few additional well-designed long term controlled studies are needed to confirm these findings, and to clarify whether any beneficial effect on diabetic retinopathy is unique to gliclazide or also occurs with other oral hypoglycaemic drugs. Both newly diagnosed maturity onset diabetics as well as those previously treated with sulphonylureas respond well to gliclazide therapy. In the small comparative studies which have been reported, gliclazide was of comparable efficacy to other oral hypoglycaemic agents.     

Ibopamine (SK&F 100168) pharmacokinetics in relation to the timing of meals.

The effect of the timing of a standard meal relative to a single oral dose of 200 mg ibopamine, on the appearance of its pharmacologically active metabolite, epinine, in plasma was investigated in a randomised crossover study in 12 healthy volunteers. After a 12 h fast, ibopamine was administered either in the fasting state (no meal), or 1 h before, 0.5 h before, immediately after, 2 h after or 3 h after a standardised meal. Blood samples taken immediately before and at intervals for 3 h after dosing were analysed for free epinine. Maximum concentration (Cmax), time to Cmax(tmax), and area under the concentration-time curve (AUC) for free epinine in plasma were calculated. When compared with the fasting state, Cmax and AUC0-3h were significantly reduced when ibopamine was given immediately after or 2 h after a meal. AUC was also reduced for ibopamine given 0.5 h before a meal. tmax was significantly delayed when ibopamine was given immediately after, or 2 or 3 h after a meal. Thus, administration of ibopamine with or shortly after a meal reduced the rate and extent of appearance of free epinine in plasma. The clinical significance of reduced epinine levels on acute dosing in the presence of food is unknown.     

Glipizide increases plasma insulin but not C-peptide level after a standardized breakfast in type 2 diabetic patients

Summary Peripheral blood glucose, plasma insulin and C-peptide levels were investigated after giving a standardized breakfast (500 kcal, 60g carbohydrates) to 10 nonobese Type 2 diabetic patients previously treated by diet alone. Each patient received at random, at 1 week intervals, either 5 mg glipizide (meal + glipizide) or a placebo (meal alone) 30 min before breakfast. Basal values of blood glucose, plasma insulin and C-peptide were similar on both occasions. After meal + glipizide, the blood glucose increase was sharply limited whereas the rise in plasma insulin was steeper and reached twice as high a level. In contrast, the rise in plasma C-peptide was similar in both conditions. Consequently, the areas under the curves (0–300 min) showed a marked reduction in blood glucose after meal + glipizide (2289±149 versus 3101±169 mmol·min/l; 2p<0.001), associated with a significant increase in plasma insulin (14219±3261 versus 7591±1173 µU·min/ml; 2p<0.025) but no significant change in plasma C-peptide (342±45 versus 326±34 pmol·min/ml; N.S.). The insulin/C-peptide molar ratio was thus significantly increased after meal + glipizide (0.41±0.06 versus 0.23±0.04 at the 60th min; 2p<0.02). The dissociation between the responses of insulin and C-peptide suggests that a single dose of 5 mg glipizide in Type 2 diabetic subjects may enhance availability of peripheral insulin by extrapancreatic mechanism(s). This phenomenon may result in a higher circulating level of the hormone and therefore represent a further mode of action of sulphonylureas. Finally, the usual concept that peripheral insulin levels reflect true insulin secretion may be misleading in studies dealing with sulphonylureas.     

Time effects of food intake on the pharmacokinetics and pharmacodynamics of quazepam

AIMS: There is little information on interaction between food and the hypnotic agent quazepam. We therefore studied the effects of food and its time interval on the pharmacokinetics and pharmacodynamics of quazepam. METHODS: A randomized three-phase crossover study with 2-week intervals was conducted. Nine healthy male volunteers took a single oral 20 mg dose of quazepam under the following conditions: 1) after fasting overnight; 2) 30 min after eating standard meal; or 3) 3 h after eating the same meal. Plasma concentrations of quazepam and its metabolite, 2-oxoquazepam and psychomotor function using the Digit Symbol Substitute Test (DSST), Stanford Sleepiness Scale (SSS) and Visual Analogue Scale were measured up to 48 h. RESULTS: During the food treatments at 30 min and 3 h before dosing, the peak concentrations (Cmax) were 300% (95% CI 260, 340%; P < 0.001) and 250% (95% CI 210, 290%; P < 0.01) of the corresponding value during the fasting phase. For quazepam, the area under the plasma concentration-time curve from 0 to 8 h measured at 30 min and 3 h before dosing was significantly increased, with the food treatments by 2.4-fold (95% CI 2.0; 2.8-fold; P < 0.001) and 2.1-fold (95% CI 1.7; 2.4-fold; P < 0.01), respectively. In response to pharmacokinetic changes, some of the pharmacodynamics (DSST, P < 0.05; SSS, P < 0.05) differed significantly between fasted status and fed status. No difference was found in any pharmacokinetic or pharmacodynamic parameters between the two food treatment phases. CONCLUSIONS: A food effect on quazepam absorption is evident and continues at least until 3 h after food intake. The dosing of quazepam after a long period of ordinary fasting might reduce its efficacy because a 3 h interval between the timing of the evening meal and bedtime administration of hypnotics is regarded as normal in daily life.     

格列齐特治疗2型糖尿病的临床疗效观察

目的 对格列齐特缓释片治疗初发2型糖尿病患者的临床疗效进行观察.方法 将118例初发2型糖尿病患者随机分为三组,分别应用格列齐特缓释片、瑞格列奈(进121)、重组人胰岛素治疗12周,测定三组受试者治疗前后的糖化血红蛋白、空腹及餐后2 h血糖,并观察低血糖事件,对测试结果进行比较.结果 格列齐特缓释片治疗组空腹和餐后2 h血糖水平与重组人胰岛素治疗组差异无统计学意义(P>0.05).格列齐特缓释片治疗组空腹血糖控制优于瑞格列奈(进口)治疗组(P<0.01).重组人胰岛素对空腹血糖的控制优于瑞格列奈(进口)组(P<0.01),但两组间餐后血糖水平无明显差异.结论 对空腹血糖、餐后2 h血糖及糖化血红蛋白的控制,格列齐特缓释片、重组人胰岛素、瑞格列奈(进口)均有较好疗效.     

Effect of KAD-1229, a novel hypoglycaemic agent,on plasma glucose levels after meal load in type 2 diabetic rats

1. The effects of KAD-1229 (a novel non-sulphonylurea agent), voglibose (an alpha-glucosidase inhibitor) and nateglinide (a non-sulphonylurea antihyperglycaemic agent) on hyperglycaemia induced by a meal load were assessed in diabetic rats. 2. KAD-1229 suppressed the increase in plasma glucose levels seen after a meal load and the area under the curve for plasma glucose levels (AUCglucose) up to 5 h after the meal load. 3. Voglibose also suppressed the increase in plasma glucose levels; however, a significant decrease in AUCglucose following voglibose was not observed. 4. Nateglinide suppressed the increase in plasma glucose levels at 30 min and 1 h after the meal load; however, plasma glucose levels was above control thereafter and the AUCglucose was not decreased. 5. The results indicate that KAD-1229 has an antihyperglycaemic effect and KAD-1229 is suggested to be a suitable agent for controlling post-prandial hyperglycaemia.     

Appropriate administration schedule of D-penicillamine for pediatric Wilson's disease patients based on urinary copper excretion

The purpose of this study was to increase the amount of copper excreted resulting from the administration of D-penicillamine(DP) in pediatric Wilson's disease(WD) patients. By measuring the urinary copper excretion after adjusting the administration schedules, the appropriate timing for DP administration was investigated. The subjects were three brothers with pediatric WD. The initial daily dose of DP was 5 mg/kg/day, and gradually increased to the maintenance dose of 20 mg/kg/day. Until the maintenance daily dose was reached, DP was administered 2 h after the morning and evening meal. After reaching the maintenance daily dose of DP, the appropriate timing for taking DP was investigated in both the morning and evening. Three schedules of DP administration were compared: 2 h after meals; 30 min before meals (with fasting); and 1 h before the morning and 1.5 before the evening meal (direction 1). The resulting urinary copper excretion on each dosing schedule was compared. Little difference was found in urinary copper excretion on the first two schedules, i.e., 2 h after meals and 30 min before meals. When DP was administered 30 min before meals, urinary copper excretion [microgram/day] was 1173 in the first brother, 918 in the second, and 875 in the third. When DP was administered according to direction 1, however, urinary copper excretion was increased significantly to 1701 in the first brother, 2701 in the second, and 3808 in the third. It is known that the efficiency of urinary copper excretion with DP administration depends on the maintenance of chelating ability after absorption from the gastrointestinal tract. Our results indicate that the excretion was lower when DP was administered 2 h after or 30 min before meals (with fasting), as recommended in the package insert. Thus to achieve better copper excretion efficiency, direction 1 is recommended for WD patients.     

The effect of food on the oral bioavailability and the pharmacodynamic actions of the insulinotropic agent nateglinide in healthy subjects

Nateglinide (Starlix, SDZ DJN 608 or A-4166), a new insulinotropic agent, is intended to be administered prior to a meal in order to improve early insulin release in non-insulin-dependent diabetes mellitus patients. The effects of a meal on the oral bioavailability and pharmacodynamic actions of nateglinide were investigated. Twelve healthy male subjects completed this randomized, single-dose, four-way crossover study in which each subject received a 60 mg dose of nateglinide 10 minutes before the start of and immediately after a high-fat breakfast meal. In addition, each subject received a single 30 and 60 mg dose of nateglinide underfasting conditions. Plasma and urine concentrations of nateglinide were determined by an HPLC method while plasma glucose and insulin concentrations were measured by standard immunoassay methods. Compared to the fasted state, administration of nateglinide 10 minutes before the meal was associated with an increase in the rate of absorption (12% increase in Cmax and 52% decrease in tmax), while there was no significant effect on the extent of absorption (AUC). Alternatively, when nateglinide was given after the meal, a food effect was observed that was characterized by a decrease in the rate of absorption: 34% decrease in Cmax and a 22% increase in tmax but no significant effect on AUC. Nateglinide was rapidly eliminated with plasma t 1/2 = 1.4 hours. Its plasma renal clearance, 20.7 ml/min, appears to be due mostly to active tubular secretion. However, only 13% to 14% of the dose is recovered as nateglinide in the urine. The 30 and 60 mg tablets were dose proportional in terms of both AUC and Cmax; both tmax and t 1/2 were dose independent. Regardless of timing, the combination of a meal and nateglinide produced a larger increase in insulin levels than did nateglinide alone. Meal-related glucose excursions were eliminated when nateglinide was taken prior to the meal. Thus, the rapid onset/short duration stimulation of insulin release by nateglinide should allow good control of prandial hyperglycemia while limiting exposure to hyperinsulinemia.     

3种治疗2型糖尿病药物的成本-效果分析

目的:比较3种治疗2型糖尿病药物的成本-效果。方法:将186例2型糖尿病患者随机分成3组,分别用阿卡波糖(A组)、二甲双胍(B组)和格列齐特(C组)治疗,并进行药物经济学成本-效果分析。结果:A、B、C组成本分别为776.62、345.55、565.28元;对空腹血糖的总有效率分别为85.5%、84.6%、86.4%,对餐后2h血糖的总有效率分别为95.2%、72.3%、77.9%;对空腹血糖的成本-效果比分别为9.08、4.08、6.54元,对餐后2h血糖的成本-效果比分别为8.16、4.78、7.26元;A、C组相对于B组对空腹血糖的增量成本-效果比分别为478.9、122.1元,对餐后2h血糖的增量成本-效果比分别为18.82、39.23元。结论:控制空腹血糖以二甲双胍为佳;控制餐后血糖或以控制餐后血糖为主时以阿卡波糖为佳。     

格列齐特、甲钴胺及其联合用药对糖尿病大鼠周围神经形态学改变及神经生长因子含量的影响

目的观察格列齐特、甲钴胺及其联合用药对糖尿病大鼠周围神经形态学改变及神经生长因子含量的影响。方法采用链脲佐菌素致糖尿病大鼠模型,以组织学方法观察药物对糖尿病大鼠坐骨神经形态学改变的影响;以酶联免疫方法测定血清中神经生长因子含量;以免疫组织化学法观察坐骨神经组织内神经生长因子的含量变化。结果格列齐特、甲钴胺及其联合用药对糖尿病大鼠坐骨神经形态学改变有保护作用;对血清神经生长因子含量减少有提高作用;对坐骨神经组织中神经生长因子的含量虽无明显影响,但对坐骨神经轴突内神经生长因子的减少有提高作用。格列齐特与甲钴胺联合应用对以上指标的改善均未发现有明显性提高。结论格列齐特、甲钴胺及其联合用药对糖尿病大鼠周围神经病变具有保护作用;与单独用药相比,格列齐特与甲钴胺联合应用未见有明显性疗效增强作用。     

Influence of the semisynthetic bile acid (MKC) on the ileal permeation of gliclazide in healthy and diabetic rats

The aim of this study is to investigate how the semisynthetic bile acid; 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate, also known as 12-monoketocholic acid (MKC) influences the ileal permeation of the antidiabetic drug gliclazide in healthy and diabetic rats. Male Wistar rats were divided into 10 groups (n = 32), of which 5 comprised healthy rats (1 to 5) and 5 diabetic rats (6 to 10). Group 1 was used to measure the permeation of gliclazide (200 mug/ml) alone (control) while in groups 2 to 5 gliclazide permeation was measured in the presence of MKC (50 mug/ml), glibenclamide (100 mug/ml), rifampicin (100 mug/ml) and verapamil (30 mug/ml), respectively, using Ussing chambers. Groups 6 to 10 were treated in the same way, after the induction of type 1 diabetes with alloxan (iv 30 mg/kg). In tissues from healthy rats, there was a 9-fold reduction in the mucosal to serosal permeation of gliclazide in the presence of MKC (p < 0.001) while glibenclamide and rifampicin reduced the permeation of gliclazide in both directions; mucosal to serosal and serosal to mucosal and verapamil had no effect. In contrast, in diabetic rats, there was no net transport of gliclazide alone or after the addition of MKC, glibenclamide, rifampicin or verapamil. The lack of any net flux of gliclazide in diabetic rats suggests the lack of action of drug transporters involved or the suppression of their expression. Furthermore, MKC-induced inhibition of mucosal to serosal unidirectional flux of gliclazide, in healthy rats, can be the result of the selective inhibition of Mrp3.     

Probiotic treatment reduces blood glucose levels and increases systemic absorption of gliclazide in diabetic rats

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.     

初发2型糖尿病胰岛素治疗剂量的门诊观察

目的：探讨门诊首次诊断糖尿病人应用胰岛素进行治疗的剂量。方法：32名门急诊糖尿病人，分别应用双相门冬氨酸胰岛素30（商品名：诺和锐30）（20例）及诺和灵30R（12例）进行血糖控制，观察血糖的变化，调整胰岛素的用量。结果：初次诊断时空腹血糖（FPG）、餐后2h血糖（PIG）两组间无统计学差异。两种胰岛素治疗1周后两组间空腹血糖（FPG）无统计学差异，而诺和锐30组餐后2h血糖（PPG）低于诺和灵30R组（P〈0．05）；达到血糖控制标准时，诺和锐30组达标时间较诺和灵30R组短（P〈0．05）；血糖控制达标后继续观察1个月，诺和锐30组胰岛素维持剂量低于诺和灵30R组（P〈0．05）。结论：对于门诊初次发现糖尿病的患者，应用诺和锐30的效果可能较诺和灵30R更加显著。