吡格列酮与盐酸罗格列酮治疗2型糖尿病疗效比较

目的：比较吡格列酮与罗格列酮治疗2型糖尿病的临床疗效.方法：60例磺酰脲类和双胍类治疗而空腹血糖控制不佳（7.0 mmol·L-1≤空腹血糖（FBG）≤13.0 mmol·L-1）的2型糖尿病患者,随机分入吡格列酮15 mg·d-1组与罗格列酮4mg·d-1组,治疗12周后比较2组疗效.结果：12周后,2组空腹和餐后2 h血糖、胰岛素和糖化血红蛋白均明显下降（P〈0.01）,但2组间差异无统计学意义（P〉0.05）.吡格列酮组总费用合计为189.84元、罗格列酮组为440.16元,2组均无严重不良反应发生.结论：吡格列酮与罗格列酮治疗2型糖尿病疗效相似,但吡格列酮的费用明显低于罗格列酮.     

盐酸吡格列酮治疗2型糖尿病有效性和安全性的临床观察

目的:评价盐酸吡格列酮联合磺脲类和二甲双胍治疗2型糖尿病患者的疗效和安全性。方法:口服磺脲类和二甲双胍药物稳定剂量1个月以上,而且空腹血糖≥7.5mmol·~(-1)的2型糖尿病患者101例,破随机双盲分入吡格列酮(每天30mg)治疗组(47例)或安慰剂联合磺脲类和二甲双胍对照组(46例),观察时间为12周。结果:吡格列酮治疗组在降低HbAlc、空腹和餐后2h血糖,都较对照组显著有效(P<0.05)。12周后,吡格列酮组空腹血糖平均下降1.6mmol·L~(-1),餐后2h血糖下降2.1mmol·L~(-1),HbAlc水平下降1.1％。吡格列酮联合磺脲类和二甲双胍治疗可明显降低甘油三酯水平(29％),同时升高HDL-C水平(11％),总胆固醇和LDL-C水平亦有降低。吡格列酮耐受性良好,药物不良反应发生率与对照组无明显差异。结论:吡格列酮联合磺脲类和二甲双胍治疗2型糖尿病可明显改善HbAlC水平和空腹、餐后2h血糖,同时对本文所观察的脂代谢指标有改善作用。     

多中心、随机、双盲、安慰剂平行对照评价盐酸吡格列酮治疗2型糖尿病的有效性和安全性的临床研究

目的评价盐酸吡格列酮对2型糖尿病患者合用磺酰脲类和双胍类药物时的降血糖作用,观察其安全性.方法采用随机、双盲、安慰剂平行对照和多中心临床研究方法.对283例应用磺脲类和双胍类治疗而血糖控制不佳(7mmol/L≤空腹血糖＜13.0mmol/L)的2型糖尿病患者随机分入吡格列酮30mg组与安慰剂组治疗随访6次共12周.结果于12周时,试验组与对照组空腹血糖水平较基线值分别平均下降了1.1和0.4mmol/L(p＜0.001);餐后血糖分别下降了1.5mmol/L和0.3 mml/L,p＜0.001;HbAlc分别下降了0.7%和0.4%(p＜0.01).试验组空腹胰岛素下降幅度高于对照组(p＜0.05),其两组治疗前后的差值比较均分别具有显著性统计学差异.试验组HOMA-IR降低(p＜0.01).结论12周的临床观察显示,对2型糖尿病患者饮食、运动和口服降糖药(磺脲类和双胍类)治疗控制不佳者联合应用吡格列酮(30mg/日),代谢控制可得到进一步的改善,胰岛素的敏感性增强,安全性和耐受性好.     

吡格列酮二甲双胍片治疗2型糖尿病的多中心随机双盲平行对照临床试验

目的 以盐酸二甲双胍和盐酸吡格列酮(均降糖药)为对照,评价吡格列酮二甲双胍片治疗2型糖尿病的疗效和安全性.方法 用多中心随机双盲双模拟阳性平行对照的试验设计,观察240例2型糖尿病病人,分为吡格列酮二甲双胍片组(试验组)和盐酸二甲双胍、盐酸吡格列酮组(对照组).结果 用药16周后,与基础值相比,试验组空腹血糖(FBG)、餐后2 h血糖(P2hBG)、糖化血红蛋白(HbAlC)分别下降(1.92±1.77)mmol·L~(-1),(2.49±3.13)mmol·L~(-1),(1.27±1.45)%;对照组,FBG、PBG、HbA1c分别下降(2.24±2.11)mmol·L~(-1),(2.89±3.71)mmol·L~(-1),(1.49±1.52)%,2组下降各指标治疗前后比较均有显著性差异;但2组间比较无显著性差异.2组不良反应发生率比较无统计学差异(10% vs 12%).结论 吡格列酮二甲双胍片是治疗2型糖尿病有效和安全的药物.     

沙格列汀或吡格列酮联合二甲双胍治疗初诊2型糖尿病临床观察

摘 要 目的： 探讨单用二甲双胍血糖未达标的初诊2型糖尿病加用沙格列汀或吡格列酮治疗的疗效及安全性。方法: 82例单用二甲双胍治疗12周血糖未达标的初诊2型糖尿病患者随机分为两组,分别联合沙格列汀或吡格列酮治疗12周,观察两组患者治疗前后血糖控制情况、胰岛素抵抗指数（HOMA-IR）、体质指数（BMI）变化及两组不良反应的差别。结果: 联合治疗12周后,两组空腹血糖(FPG)、餐后2 h血糖(2hPG)和糖化血红蛋白(HbA1c)均较治疗前明显降低（P<0.05）,沙格列汀组2hPG及HbAlc下降幅度优于吡格列酮组（P<0.05）,但FPG下降幅度小于吡格列酮组（P<0.05）。吡格列酮组空腹胰岛素水平下降及HOMA-IR的改善优于沙格列汀组（P<0.05）,沙格列汀组治疗后BMI无改变（P>0.05）,吡格列酮组治疗后BMI增加（P<0.05）;两组患者药品不良反应比较,差异无统计学意义（P>0.05）。结论:单用二甲双胍血糖控制不佳的初诊2型糖尿病患者加用沙格列汀或吡格列酮均能有效控制血糖,改善胰岛素抵抗,沙格列汀更适合于合并器质性心脏病或老年患者。     

吡格列酮对2型糖尿病患者血清C反应蛋白和肿瘤坏死因子-α的影响

目的:观察吡格列酮治疗对2型糖尿病(T2DM)患者血清炎症因子C-反应蛋白(CRP)及肿瘤坏死因子-α(TNF-α)水平的影响.方法:采用随机、双盲法将2型糖尿病患者90例分为对照组和吡格列酮组,对照组联合应用磺脲类和双胍类药物,吡格列酮组每天加服吡格列酮15 mg治疗12周,分别检测两组治疗前后空腹血糖(FPG)、2 h血糖(2 hPG)、糖化血红蛋白(HbAlc)、血清CRP、TNF-α水平,评估治疗前后胰岛素抵抗(IR)变化.结果:对照组糖化血红蛋白(HbAlc)显著下降(P＜0.01),其他指标无显著变化;吡格列酮组治疗后FPG、2hPG、HbAlc、IR显著降低(P＜0.01),血清CRP、TNF-α水平治疗后显著下降(P＜0.01),与对照组比较差异有极显著性(P＜0.01).结论:吡格列酮治疗T2DM能改善胰岛素抵抗、降低血糖,具有明显的抗炎作用.     

盐酸吡格列酮治疗2型糖尿病的疗效及安全性

目的以二甲双胍为对照,评价盐酸吡格列酮治疗2型糖尿病的疗效和安全性.方法采用多中心、随机、双盲双模拟、平行对照的试验设计,在5个中心共收集227例2型糖尿病病人,分为吡格列酮组(113例,服用盐酸吡格列酮30mg,每日1次),和二甲双胍组(¨4例,服用盐酸二甲双胍250mg,每日2次),治疗期12周.结果用药12周后,与基础值相比,吡格列酮组空腹血糖下降1.42±1.93mmo1.L-1(13.41%±18.65%),餐后2h血糖下降4.42±3.96mmo1.L-1(26.94%±21.32%),糖化血红蛋白下降0.80%±1.57%;二甲双胍组,空腹血糖下降1.62±2.17mmo1.L(15.45%±20.13%),餐后2h血糖下降值3.89±3.75mmo1.L-1(24.27%±21.54%),糖化血红蛋白下降0.89%±1.39%.两组血糖和糖化血红蛋白下降值与用药前比较均有显著性差异,但两组间比较无显著性差异.用药12周后,吡格列酮组,降低空腹血糖显效率40.66%,有效率75.82%,降低餐后2h血糖显效率51.38%,有效率86.24%二甲双胍组,降低空腹血糖显效率53.85%,有效率82.42%,降低餐后2h血糖显效率46.23%,有效率77.36%.两组间比较显效率和有效性均无统计学意义.两组药物不良反应发生率相似,未出现严重肝功能异常病例.结论吡格列酮可有效地降低2型糖尿病病人的空腹血糖、餐后2h血糖和糖化血红蛋白,耐受性好,未发生严重药物不良反应.     

吡格列酮与二甲双胍联合治疗对改善2型糖尿病胰岛素抵抗的随机对照研究

目的观察吡格列酮与二甲双胍联合治疗对2型糖尿病患者胰岛素抵抗的疗效。方法随机、平行对照的为期12周试验。吡格列酮与二甲双胍组45例,吡格列酮对照组45例。结果吡格列酮与二甲双胍组HbA1c从(8.2±2.3)%下降至(6.7±1.3)%;而对照组则从(8.1±1.4)%下降至(7.6±1.2)%,2组间有统计学差异(P<0.05)。吡格列酮与二甲双胍组HOMA-IR由(5.6±1.3)下降至(3.5±1.1);而对照组则从(5.5±1.4)下降至(4.6±1.2),2组间存在差异(P<0.05)。结论吡格列酮与二甲双胍联合治疗较单用吡格列酮可进一步控制血糖并减轻胰岛素抵抗。     

盐酸吡格列酮对2型糖尿病患者的长期疗效及安全性探讨

目的观察吡格列酮对2型糖尿病（T2DM）患者的长期疗效及安全性。方法36例使用用磺酰脲类及双胍类药物治疗3个以上月血糖控制不佳的T2DM患者,加服盐酸吡格列酮随访24个月,观察治疗前后空腹血糖（FPG）、餐后两小时血糖（2HPG）、糖化血红蛋白（HbA1c）,空腹胰岛素（FInS）,HoMA-IR,血清高敏C反应蛋白（hsC-Rp）,血红蛋白（Hb）和谷丙转氨酶（GPT）等变化。结果盐酸吡格列酮治疗后FPG、2HPG、HbA1c、Fins、hsCRP均较治疗前明显下降（P〈0．01）,GPT亦较治疗前下降（P〈0．05）。不良反应为下肢浮肿,发生率为2．8％,经对症处理后消失。结论盐酸吡格列酮能有效降低其他口服降糖药物控制不佳的T2DM患者的血糖水平,对因脂肪肝所致的GPT增高有降低作用,有良好的安全性。     

盐酸吡格列酮治疗2型糖尿病的多中心临床研究

目的　评价盐酸吡格列酮治疗2型糖尿病的有效性及安全性。方法　用多中心随机双盲平行对照方法,将已合用磺脲类和双胍类药物的2型糖尿病患者随机分为2组:试验组口服吡格列酮,每日30mg;对照组服用安慰剂。各118例,疗程12周。结果　试验组空腹血糖、餐后2h血糖有明显下降(P<0. 01);糖化血红蛋白2组均有下降,试验组为-1. 06%,对照组为-0. 51%,均P<0. 01。2组胰岛素水平均无明显变化。治疗后,试验组高密度脂蛋白胆固醇升高了0. 11mmol·L-1 (P<0. 01),低密度脂蛋白胆固醇下降了0. 21mmol·L-1(P<0. 01),血压下降有统计学意义(P<0. 01),体重指数升高了0. 36 (P<0. 01)。试验组中,仅1例因中度肝功能异常退出试验,水肿较常见,程度轻。其他不良事件发生率2组相近。结论　口服降糖药后血糖控制不佳的2型糖尿病患者,加用盐酸吡格列酮30mg,可显著降低血糖,提高胰岛素敏感性,改善高血压状态,病人耐受性较好。     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Penetration and action of edoxudine in vitro and in vivo

The penetration of 5-ethyl-2'-deoxyuridine (edoxudine, Aedurid) from gel base with and without the addition of urea and other adjuvant has been studied in an in vitro model using guinea pig skin. The formulation of 3% edoxudine gel with 5% urea showed the best results. In vivo experiments on hairless mice infected intracutaneously with herpes simplex virus type 1 also showed this formulation's good efficacy as compared to other formulations.     

Extraction and determination of prednisolone in drugs and excipients in ointments and creams and the uniformity of distribution in prednisolone ointment

For the purpose of measuring the contents of prednisolone in low concentrated ointments and creams an instruction was elaborated that includes several steps of extraction, in the resulting solution of which the assay of the steroid by Blue Tetrazolium reaction will be done. The procedure permits the determination of prednisolone in presence of most of usual ingredients of ointment bases except wool alcohols. Also no influence is given by some remedies combined with prednisolone for topical application except coal tar solution. The results confirm a correct reflection of the steroid contents declared respectively the recovery of the steroid added to various ointment bases. Introducing discussion to content uniformity concerning low concentrated ointments is made, and some deviations are shown.     

Mechanisms of antiplatelet and antithrombotic activity of midazolam in in vitro and in vivo studies

Dopamine regulates various physiological functions in the central nervous system and the periphery. Dysfunction of the dopamine system is implicated in a wide variety of disorders and behaviors including schizophrenia, addiction, and attention-deficit hyperactivity disorder. Medications that modulate dopamine signaling have therapeutic efficacy on the treatment of these disorders. However, the causes of these disorders and the role of dopamine are still unclear. Studying the dopamine system in a model organism, such as Caenorhabditis elegans, allows the genetic analysis in a simple and well-described nervous system, which may provide new insight into the molecular mechanisms of dopamine signaling. In this review, we summarize recent findings on pharmacological and biochemical properties of the C. elegans dopamine receptors and their physiological role in the control of behavior.     

Comparative in vivo and in vitro studies of phenytoin protein binding and in vitro lipolysis in plasma of pregnant and nonpregnant rats

This investigation was designed to determine the cause of the changes in drug protein binding that occur in rat plasma, particularly in plasma from pregnant animals, during in vitro drug-protein binding measurements. In vivo estimates of phenytoin binding in plasma were obtained from steady-state CSF-plasma concentration ratios in pregnant and nonpregnant rats. Immediate ultrafiltration of heparin- or EDTA-anticoagulated plasma yielded phenytoin free fraction values that were in good agreement with in vivo estimates for nonpregnant rats but that were about one-third higher than in vivo estimates for pregnant animals. In vitro free fraction values tended to increase during incubation of plasma and/or during equilibrium dialysis. The concentrations of the four major endogenous free fatty acids were similar in plasma of pregnant and nonpregnant rats if determined immediately after blood collection. Six hours of incubation at 37 degrees C caused fatty acid concentrations to increase about fivefold and twofold in heparin-anticoagulated plasma from pregnant and nonpregnant animals, respectively. The corresponding increases in EDTA-anticoagulated plasma were only about twofold and 1.14-fold, respectively. These changes were associated with decreased plasma protein binding of phenytoin. The in vivo differences between pregnant and nonpregnant rats with respect to phenytoin binding in plasma are not due to differences in fatty acid concentrations, but the in vitro differences are due primarily to corresponding differences in free fatty acid concentrations if extensive in vitro lipolysis occurs.     

Comparison of in vitro and in vivo developmental toxicity and pharmacokinetics of phenytoin in the rat

The rat whole embryo culture was compared to an in vivo experiment with regard to embryotoxicity as well as exposure characteristics, using phenytoin as a model compound. Intra-embryonic concentrations and their embryotoxic effects were determined on gestation day 11 after in vitro administration of 50-150 microg/ml or in vivo gavage of 500-1500 mg/kg body-weight on gestation day 10. In addition, exposure kinetics were studied in vivo after a single oral dose on gestation day 10, and developmental defects on gestation day 21 were scored. The embryotoxic effects observed on gestation day 11 were more pronounced after in vitro exposure in comparison to in vivo exposure at similar intra-embryonic concentrations. Exposure of phenytoin on gestation day 10 in vitro via the culture medium resulted in general embryotoxicity on gestation day 11, whereas in vivo effects as determined on gestation day 11 were minimal. Plasma concentrations of phenytoin increased and plateaued around 35 microg/ml during the 48 hr monitoring period. Plasma concentration curves and pharmacokinetic parameters did not show remarkable differences between the dose groups, indicating that absorption is the limiting factor at the dose range used. Although the developmental effects were minimal as observed in vivo on gestation day 11, specific malformations (defects encompassing the urogenital. craniofacial and skeletal systems) were observed on gestation day 21. These findings show that with similar intra-embryonic concentrations of phenytoin the embryotoxicity in rat whole embryo culture was not comparable with the in vivo embryotoxicity as determined on gestation day 11. This discrepancy may at least partly be explained by differences in exposure characteristics.     

Mathematical modelling of in situ and in vitro efflux of ciprofloxacin and grepafloxacin

The efflux process due to p-glycoprotein-like mechanisms of ciprofloxacin (CIP) and grepafloxacin (GRX) has been studied "in situ" in rats and "in vitro" in Caco-2 cells. The results were modelled by a curve fitting procedure which allowed the characterization of the passive (Pd) and carrier mediated parameters (Vm and Km) from the raw data without initial velocities estimation. CIP absorption in rat was characterized as a passive diffusion at the assayed concentrations. Although the involvement of an efflux transporter cannot be ruled out, its relevance in the transport of the fluoroquinolone is negligible. In GRX absorption, an efflux process is implicated and it is detected in both absorption models. GRX permeability depends on the intestinal segment, reflecting the previously reported different expression level of the efflux transporters along the gut in rat. A first attempt to correlate the "in vitro" and the "in situ" data has been done. The mathematical model has been constructed using very simplistic assumptions and it will require further refinement but, nevertheless, the results are promising and demonstrate that a good modelling approach helps to identify the system critical parameters and how the system behaviour change when the parameters are modified as it happens when we move from the "in vitro" to the "in situ" level. Predicted versus experimental permeability values show a good correlation, demonstrating that the relevance of the secretion process "in situ" in rat can be predicted from the "in vitro" cell results.     

Comparison of pulmonary and hepatic glucuronidation and sulphation of ethanol in rat and rabbit in vitro

1. Pulmonary and hepatic UDP-glucuronyltransferase and sulphotransferase activities in subcellular fractions from rats and rabbits were determined, comparing ethanol with known substrates for these enzymes.

2. No ethyl glucuronide formation was detected with either hepatic or pulmonary microsomal incubations.

3. Chromatographic, autoradiographic and scintillation counting analysis indicated that ethanol is sulphated by rat and rabbit pulmonary cytosol, although this activity was approx. 2–6% of that in liver.

4. Rat hepatic and pulmonary sulphotransferase activities with β-naphthol were approx. 13 and 60 times higher than with ethanol, respectively.

5. Rabbit hepatic and pulmonary sulphotransferase activities with both substrates were higher than those in rat.