优泌乐25病例

优泌乐25治疗老年2型糖尿病临床观察王国焕;张颖【期刊名称】《浙江中西医结合杂志》【年(卷),期】2013(000)005【总页数】3页(P383-384,385)【关键词】老年人;糖尿病;优泌乐25【作者】王国焕;张颖【作者单位】浙江省绍兴市安康医院绍兴 312000;浙江省绍兴市第二医院内分泌科【正文语种】中文糖尿病治疗过程中，常常要兼顾老年人体质特点。

笔者对预混胰岛素类似物优泌乐25和重组胰岛素优泌林治疗2型糖尿病进行比较，观察两种方案治疗老年糖尿病的疗效和安全性。

1 临床资料1.1 一般资料选择2009年8月—2011年10月间本院住院60岁以上初诊老年2型糖尿病住院患者98例，未曾服用过降糖药物。

随机分为优泌乐25组51例，男26例，女25例，年龄0.5～78.6岁，平均（68.4±6.4）岁；平均病程（7.8±2.1）年；体质指数（BMI）（23.1±1.4）kg/m2，空腹血糖（11.2±2.7）mmol/L。

优泌林组47例，男25例，女22例，年龄(61.6～82.1)岁，平均(69.2±8.9)岁；平均病程（6.7±2.3）年；BMI（22.4±1.8）kg/m2，空腹血糖（10.8±1.9）mmol/L。

两组年龄、病程、BMI、空腹血糖比较差异无统计学意义（P均＞0.05），具有可比性。

1.2 诊断标准诊断均符合1999年WHO制定的糖尿病诊断标准[1]。

排除：1型糖尿病；严重的心、肺、肝、肾功能不全者及服用免疫抑制剂、激素等影响血糖药物者。

2 治疗方法两组患者均控制饮食及运动，不服用磺脲类降糖药，睡前少吃粮食制品。

优泌乐组三餐前即刻皮下注射优泌乐25，起始剂量：早餐前8U，中餐前4U，晚餐前8U，逐步调整；优泌林组，三餐前30min注射优泌林R，起始剂量各6U；晚8点注射优泌林N，起始剂量为4U，逐步调整。

优泌乐25治疗2型糖尿病的临床观察刘美茹赵向晖【摘要】目的观察优泌乐25治疗2型糖尿病的临床疗效。

方法选择52例需胰岛素治疗的2型糖尿病患者，随机分为两组，A组为优泌乐25组，B组为优泌林70/30组，治疗12周。

结果两组治疗后空腹血糖控制水平相似，A组餐后2h血糖控制优于B组，且HbA1c下降较B组明显，胰岛素用量少，低血糖发生率低。

结论优泌乐25可以更加有效地控制餐后血糖，减少低血糖发生，安全性好。

【关键词】优泌乐25；2型糖尿病本研究对口服降糖药物继发失效的2型糖尿病患者采用优泌乐25日2次皮下注射，并与预混人胰岛素比较，观察临床疗效。

1资料与方法1.1一般资料选择2009年6月至2011年10月在辽宁省盘锦市中心医院内分泌科住院的2型糖尿病患者52例，均符合1999年WHO糖尿病诊断标准，入选前均口服降糖药物，未曾使用胰岛素治疗。

年龄32 55岁，男性28例，女性24例，病程3 14年，排除严重心、肝、肾功能不全，无急性并发症及应激因素。

两组患者在性别、年龄、病程、BMI、治疗前血糖水平及糖化血红蛋白等方面无统计学差异，具有可比性。

1.2方法两组患者均停用原口服降糖药物，给予同等的糖尿病知识教育，并进行饮食管理，A组改为优泌乐25注射液，早、晚餐前皮下注射，B组给予优泌林70/30注射液，早、晚餐前30min皮下注射，起始剂量均为0.4 0.5U/（kg·d），治疗12周。

采用强生稳豪血糖仪，每天测全天血糖（3餐前及3餐后2h，凌晨3时），达标后每周1次全天血糖监测，有低血糖症状的随时查血糖并记录，出院后每周门诊随访1次，根据血糖监测值调整药物用量。

目标血糖值FPG4.4 6.1mmol/L，2hPG4.4 8.0mmol/L，血糖﹤3.9mmol/L定义为低血糖。

1.3观察指标观察两组治疗前后空腹血糖、餐后2h血糖、HbA1c、胰岛素用量、低血糖发生次数等指标，进行统计学分析。

盐酸二甲双胍缓释片联合优泌乐25治疗2型糖尿病30例临床观察发表时间：2016-04-19T16:33:26.280Z 来源：《医师在线》2015年12月第24期供稿作者：王雪芹[导读] 优泌乐25在餐前即刻注射或餐后立即注射，极大方便了快捷奏的患者；也为进餐时间不固定的患者提供了新的选择。

王雪芹摘要目的：探讨盐酸二甲双胍缓释片联合优泌乐25治疗2型糖尿病(T2DM)患者的临床疗效及不良反应。

方法：对30例盐酸二甲双胍缓释片联合优泌乐25治疗的T2DM患者进行回顾性总结分析。

疗程三个月，观察治疗前后血糖(FBG、2hBG)、糖化血红蛋白(HbAIc)、血脂、肝肾功能、体重的变化及付作用。

结果：治疗3个月后，FBG、2hBG、HbAlc、TG均显著下降(p<0.001),肝肾功能、体重无变化；3例低血糖反应，4例轻度恶心，未停药。

结论：盐酸二甲双胍缓释片联合优泌乐25治疗T2DM效果显著，付作用小，减少胰岛素用量，体重不增加，值得临床推广。

关键词盐酸二甲双胍缓释片优泌乐252型糖尿病(T2DM)是常见的慢性代谢性疾病，胰岛β细胞功能进行性损伤和胰岛素抵抗干扰了`治疗效果，我们于2011年5月-2012年5月用盐酸二甲胍缓释片联合优泌乐25治疗T2DM效果较好，现报告如下：1资料与方法1．1一般资料：全部30例T2DM来自糖尿病门诊，符合1999年世界卫生组织(WHO)制定的T2DM诊断标准(1)。

均经饮食、运动管理及口服降糖药治疗控制不佳的T2DM患者。

排除标准：①T1DM 、妊娠糖尿病、糖尿病急性并发症、心、肝肾功能不全，②有感染和应激等。

其中男性14例，女性16例，年龄45-70岁，平均55.6±2.1,病程1-20年，平均7.4±1.2年。

血糖FBG 8.3-15.4MMOL/l,2hBG 12.3-22.5mmol/L HbAlc>10%。

1．2治疗方法 30例T2DM患者全部停用原口服磺脲类及其它降糖药，进行糖尿病教育，制定科学食谱、合理的有氧运动计划，优泌乐25采用早晚餐前即刻皮下注射，起始剂量为0.3-0.5u(/kg.d),每周来院测FBG、2hBG(平时可在家监测)，根据血糖调整胰岛素剂量，盐酸二甲双胍缓释片0.5g早进餐时口服，直至血糖达标。

优泌乐50与优泌乐25降餐后血糖的临床分析摘要目的观察优泌乐50与优泌乐25治疗糖尿病降低餐后血糖水平的临床效果。

方法选取63例糖尿病患者，随机分为实验组（32例）和对照组（31例）。

两组患者均予以常规饮食治疗和健康教育，在此基础上观察组给予优泌乐50餐前皮下注射，对照组给予优泌乐25餐前皮下注射，连续1周记录两组患者注射优泌乐后餐后血糖的变化情况，分析比较优泌乐50与优泌乐25降低餐后血糖的临床效果。

结果两组患者治疗1周后的空腹血糖水平均降低，但差异无统计学意义（P>0.05），治疗后两组患者的日常三餐的餐后2 h血糖水平也均降低，观察组患者餐后血糖水平明显低于对照组，差异具有统计学意义（P ＜0.05）。

结论优泌乐50降低餐后血糖水平的效果明显较优泌乐25优越。

关键词糖尿病；优泌乐50；优泌乐25；餐后血糖Clinical analysis of Humalog 50 and Humalog 25 for regulating postprandial blood glucose LI Lan-sheng. Nanjing City Pukou District Puchang Hospital，Nanjing 210031，China【Abstract】Objective To observe clinical effect of Humalog 50 and Humalog 25 for treating diabetes mellitus and regulating postprandial blood glucose. Methods A total of 63 diabetes mellitus patients were randomly divided into experimental group （32 cases）and control group （31 cases）. Both groups received conventional dietary therapy and health education. The observation group received additional Humalog 50 by preprandial subcutaneous injection，and the control group received Humalog 25 by preprandial subcutaneous injection. Changes of postprandial blood glucose after injection of Humalog were recorded for 1 week in the two groups. Results Both groups had decreased fasting blood glucose after 1 week of treatment，but their difference had no statistical significance （P>0.05）. They also had decreased 2 h postprandial blood glucose after daily meals. The observation group had much lower level of postprandial blood glucose than the control group，and their difference had statistical significance （P＜0.05）. Conclusion Humalog 50 provides remarkably better effect in regulating postprandial blood glucose than Humalog 25.【Key words】Diabetes mellitus；Humalog 50；Humalog 25；Postprandial blood glucose糖尿病是目前危害人类健康三大慢性疾病的其中之一，随着生活水平的提高和环境因素的改变，糖尿病的发病率逐年提高。

HEILONGJIANG MEDICIAE AND PHARMACY Feb.0077,Vol.44No.1•71・优泌乐25联合胰岛素增敏剂治疗2型糖尿病疗效分析①司雯雯（河南科技大学第一附属&隐第一药房，河南洛阳47709）摘要：目的：探讨优泌乐25联合胰岛素增敏剂治疗磺D类药物继发失效7型糖尿病患者的临床疗效。

方法:选取我院7型糖尿病患者708例，随机数字表法分为观察组（/=54）、对照组（/=54），对照组采用优泌乐25治疗，观察组于对照组基础上联合胰岛素增敏剂治疗。

比较两组治疗前后血糖［餐后2h血糖（27PG）、糖化血红蛋>（H9A7c）、空腹血糖（FPG）］水平及胰岛功能［胰岛素抵抗指数（HOMA-IR）、胰岛0细胞功能指数（HOMA-0）、空腹胰岛素（FINS）］水平。

结果：治疗17周后,观察组2hPG、H9A7c、FPG、HOMA-IR水平低于对照组，FINS、HOMA-0水平高于对照组（P<0.05）。

结论：优泌乐25联合胰岛素增敏剂治疗磺D类药物继发失效2型糖尿病患者疗效显著,可改善患者胰岛功能，有效控制其血糖水平。

关键词：优泌乐25；胰岛素增敏剂；继发性失效2型糖尿病;胰岛功能中图分类号:R587.1文献标识码:B文章编号：1008-074（2021）07-077-02近年来,2型糖尿病发病率呈逐年上升趋势，若未及时有效治疗，血糖水平长期升高可诱发糖尿病视网膜病变、糖尿病肾病、神经病变等，严重危及患者生命安全71o磺7类药物为临床治疗2型糖尿病常用药物，据报道,采用磺7类药物治疗的2型糖尿病患者，每年约5%出现继发性失效,针对此类患者应采取何种方案治疗已成为研究热点71o优泌乐25由75%精蛋白胰岛素、25%赖脯胰岛素组成，可于餐前或进餐时皮下注射,可显著降低餐后血糖,调节血糖浓度。

胰岛素增敏剂为过氧化物酶增殖体激活受体激动剂，可增强机体胰岛素敏感性，抑制胰岛素抵抗，促使胰岛素充分发挥作用，已广泛应用于临床治疗中71o基于此，本研究选取75例磺7类药物继发性失效2型糖尿病患者，旨在探究优泌乐29联合胰岛素增敏剂的临床治疗效果。

表1伴冠心病患者的临床特点一般资料A组（n=83）B组（n=151）性别（男/女）52/3187/64年龄（岁）68.1ʃ4.865.4ʃ5.71）病程7.2ʃ4.7 5.8ʃ2.92）吸烟n（%）19（22.89）28（18.54）BMI27.4ʃ3.524.2ʃ3.11）SBP（mmHg）140.1ʃ9.6138.7ʃ6.1DBP（mmHg）80.8ʃ7.178.5ʃ6.32）TC 6.48ʃ2.52 5.91ʃ3.592）TG 1.83ʃ0.25 1.74ʃ0.682）HDL－C0.61ʃ0.250.94ʃ0.651）LDL－C 3.87ʃ0.84 3.15ʃ0.461）APO－A1 1.27ʃ0.24 1.38ʃ0.74APO－B 1.58ʃ0.43 1.45ʃ0.64FBG8.3ʃ2.68.5ʃ1.8P2BG18.7ʃ3.117.4ʃ3.61）HbA1c7.26ʃ1.087.15ʃ1.12UA314ʃ57.1268ʃ41.91）Hs－CRP9.1ʃ5.38.5ʃ5.9注：与A组比较，1）P＜0.01，2）P＜0.05。

聚集与溶解。

（2）尿酸可促进LDL氧化和脂质过氧化，并伴随氧自由基生成的增加，参与到炎性反应中。

（3）参与血小板的活化与聚集，导致血栓形成。

有资料显示，高尿酸血症可引起脂代谢紊乱，使生长激素的作用增加，导致动脉斑块和血管壁细胞增生［4］。

但也有研究认为血尿酸升高不能作为冠心病的独立危险因素，在缺乏其他代谢异常存在时，血尿酸升高可能与冠心病的发生有关［5］。

有研究发现：2型糖尿病患者血清C－反应蛋白水平较常人为高，而体内C－反应蛋白水平较高者更易发展成为冠心病［6］。

我们的研究结果显示并发冠心病在年龄，病程，体重指数，舒张压，血脂，餐后2小时血糖，血尿酸密切相关。

参考文献1.中国心脏调查组．中国住院冠心病患者糖代谢异常研究———中国心脏调查．中华内分泌代谢杂志2006；22：7－10．2．张化冰，向红丁，杨玉芝，等．十五省市1991－2005年住院糖尿病病人死因调查．中国糖尿病杂志2009；17（1）：6－8．3．Prior J O，Quiňones M J，Hernadez－Pampalon M，et al．Coronary Circulatory Dysfunction in Insulin Resistance，Impaired Glu-cose Tolerance and Type2Diabetes Mellitus．Circulation2005；111：2291－2298．4．李彪，齐海梅，裕东洁，等．老年人群慢性肾脏疾病流行病学研究．中华老年医学杂志2009；28（3）：250－253．5．苏工，米树华，陶红，等．代谢综合征患者血尿酸水平与冠心病的关系．中华内分泌代谢杂志2005；21（1）：66－67．6．潘云红．冠心病合并2型糖尿病患者C反应蛋白和尿酸的变化．临床内科杂志2010；27（6）：428．（2011—04—28收稿）优泌乐25联合二甲双胍治疗2型糖尿病30例疗效分析乌鲁木齐市第一人民医院（830011）孙燕古兰贝尔摘要30例T2DM在合理饮食、适当运动定期监测血糖等措施的基础上给予优泌乐25联合二甲双胍口服治疗。

PV 5551 AMPHUMALOG® Mix75/25TM75% INSULIN LISPRO PROTAMINE SUSPENSION AND25% INSULIN LISPRO INJECTION(rDNA ORIGIN)100 UNITS PER ML (U-100)DESCRIPTIONHumalog® Mix75/25™ [75% insulin lispro protamine suspension and 25% insulin lispro injection, (rDNA origin)] is a mixture of insulin lispro solution, a rapid-acting blood glucose-lowering agent and insulin lispro protamine suspension, an intermediate-acting blood glucose-lowering agent. Chemically, insulin lispro is Lys(B28), Pro(B29) human insulin analog, created when the amino acids at positions 28 and 29 on the insulin B-chain are reversed. Insulin lispro is synthesized in a special non-pathogenic laboratory strain of Escherichia coli bacteria that has been genetically altered to produce insulin lispro. Insulin lispro protamine suspension (NPL component) is a suspension of crystals produced from combining insulin lispro and protamine sulfate under appropriate conditions for crystal formation.Insulin lispro has the following primary structure:Insulin lispro has the empirical formula C257H383N65O77S6 and a molecular weight of 5808, both identical to that of human insulin.Humalog Mix75/25 vials and Pens contain a sterile suspension of insulin lispro protamine suspension mixed with soluble insulin lispro for use as an injection.Each milliliter of Humalog Mix75/25 injection contains insulin lispro 100 units, 0.28 mg protamine sulfate, 16 mg glycerin, 3.78 mg dibasic sodium phosphate, 1.76 mg Metacresol, zinc oxide content adjusted to provide 0.025 mg zinc ion, 0.715 mg phenol, and Water for Injection. Humalog Mix75/25 has a pH of 7.0 to 7.8. Hydrochloric acid 10% and/or sodium hydroxide 10% may have been added to adjust pH.CLINICAL PHARMACOLOGYAntidiabetic ActivityThe primary activity of insulin, including Humalog Mix75/25, is the regulation of glucose metabolism. In addition, all insulins have several anabolic and anti-catabolic actions on many tissues in the body. In muscle and other tissues (except the brain), insulin causes rapid transport of glucose and amino acids intracellularly, promotes anabolism, and inhibits protein catabolism. In the liver, insulin promotes the uptake and storage of glucose in the form of glycogen, inhibits gluconeogenesis, and promotes the conversion of excess glucose into fat.Insulin lispro, the rapid-acting component of Humalog Mix75/25, has been shown to be equipotent to Regular human insulin on a molar basis. One unit of Humalog® has the sameglucose-lowering effect as one unit of Regular human insulin, but its effect is more rapid and of shorter duration. Humalog Mix75/25 has a similar glucose-lowering effect as compared with Humulin® 70/30 on a unit for unit basis.PharmacokineticsAbsorption — Studies in nondiabetic subjects and patients with type 1 (insulin-dependent) diabetes demonstrated that Humalog, the rapid-acting component of Humalog Mix75/25, is absorbed faster than Regular human insulin (U-100). In nondiabetic subjects given subcutaneous doses of Humalog ranging from 0.1 to 0.4 U/kg, peak serum concentrations were observed 30 to 90 minutes after dosing. When nondiabetic subjects received equivalent doses of Regular human insulin, peak insulin concentrations occurred between 50 to 120 minutes after dosing. Similar results were seen in patients with type 1 diabetes.Figure 1: Serum Immunoreactive Insulin (IRI) Concentrations, After Subcutaneous Injection of Humalog Mix75/25 or Humulin 70/30 in Healthy Nondiabetic Subjects. Humalog Mix75/25 has two phases of absorption. The early phase represents insulin lispro and its distinct characteristics of rapid onset. The late phase represents the prolonged action of insulin lispro protamine suspension. In 30 healthy nondiabetic subjects given subcutaneous doses(0.3 U/kg) of Humalog Mix75/25, peak serum concentrations were observed 30 to 240 minutes (median, 60 minutes) after dosing (see Figure 1). Identical results were found in patients with type 1 diabetes. The rapid absorption characteristics of Humalog are maintained with Humalog Mix75/25 (see Figure 1).Figure 1 represents serum insulin concentration versus time curves of Humalog Mix75/25 and Humulin 70/30. Humalog Mix75/25 has a more rapid absorption than Humulin 70/30, which has been confirmed in patients with type 1 diabetes.Distribution — Radiolabeled distribution studies of Humalog Mix75/25 have not been conducted. However, the volume of distribution following injection of Humalog is identical to that of Regular human insulin, with a range of 0.26 to 0.36 L/kg.Metabolism — Human metabolism studies of Humalog Mix75/25 have not been conducted. Studies in animals indicate that the metabolism of Humalog, the rapid-acting component of Humalog Mix75/25, is identical to that of Regular human insulin.Elimination — Humalog Mix75/25 has two absorption phases, a rapid and a prolonged phase, representative of the insulin lispro and insulin lispro protamine suspension components of the mixture. As with other intermediate-acting insulins, a meaningful terminal phase half-life cannot be calculated after administration of Humalog Mix75/25 because of the prolonged insulin lispro protamine suspension absorption.PharmacodynamicsStudies in nondiabetic subjects and patients with diabetes demonstrated that Humalog has a more rapid onset of glucose-lowering activity, an earlier peak for glucose-lowering, and a shorter duration of glucose-lowering activity than Regular human insulin. The early onset of activity of Humalog Mix75/25 is directly related to the rapid absorption of Humalog. The time course of action of insulin and insulin analogs, such as Humalog (and hence Humalog Mix75/25), may vary considerably in different individuals or within the same individual. The parameters of Humalog Mix75/25 activity (time of onset, peak time, and duration) as presented in Figures 2 and 3 should be considered only as general guidelines. The rate of insulin absorption and consequently the onset of activity is known to be affected by the site of injection, exercise, and other variables (see General under PRECAUTIONS).In a glucose clamp study performed in 30 nondiabetic subjects, the onset of action and glucose-lowering activity of Humalog, Humalog® Mix50/50™, Humalog Mix75/25, and insulin lispro protamine suspension (NPL component) were compared (see Figure 2). Graphs of mean glucose infusion rate versus time showed a distinct insulin activity profile for each formulation. The rapid onset of glucose-lowering activity characteristic of Humalog was maintained in Humalog Mix75/25.In separate glucose clamp studies performed in nondiabetic subjects, pharmacodynamics of Humalog Mix75/25 and Humulin 70/30 were assessed and are presented in Figure 3. Humalog Mix75/25 has a duration of activity similar to that of Humulin 70/30.Figure 2: Insulin Activity After Injection of Humalog, Humalog Mix50/50, Humalog Mix75/25, or Insulin Lispro Protamine Suspension (NPL Component) in 30 NondiabeticSubjects.Figure 3: Insulin Activity After Injection of Humalog Mix75/25 and Humulin 70/30 inNondiabetic Subjects.Figures 2 and 3 represent insulin activity profiles as measured by glucose clamp studies in healthy nondiabetic subjects.Figure 2 shows the time activity profiles of Humalog, Humalog Mix50/50, HumalogMix75/25, and insulin lispro protamine suspension (NPL component).Figure 3 is a comparison of the time activity profiles of Humalog Mix75/25 (see Figure 3a) and of Humulin 70/30 (see Figure 3b) from two different studies.Special PopulationsAge and Gender — Information on the effect of age on the pharmacokinetics of HumalogMix75/25 is unavailable. Pharmacokinetic and pharmacodynamic comparisons between men and women administered Humalog Mix75/25 showed no gender differences. In large Humalog clinical trials, sub-group analysis based on age and gender demonstrated that differences between Humalog and Regular human insulin in postprandial glucose parameters are maintained across sub-groups.Smoking — The effect of smoking on the pharmacokinetics and pharmacodynamics of Humalog Mix75/25 has not been studied.Pregnancy — The effect of pregnancy on the pharmacokinetics and pharmacodynamics of Humalog Mix75/25 has not been studied.Obesity — The effect of obesity and/or subcutaneous fat thickness on the pharmacokinetics and pharmacodynamics of Humalog Mix75/25 has not been studied. In large clinical trials, which included patients with Body Mass Index up to and including 35 kg/m2, no consistent differences were observed between Humalog and Humulin® R with respect to postprandial glucose parameters.Renal Impairment — The effect of renal impairment on the pharmacokinetics and pharmacodynamics of Humalog Mix75/25 has not been studied. In a study of 25 patients with type 2 diabetes and a wide range of renal function, the pharmacokinetic differences between Humalog and Regular human insulin were generally maintained. However, the sensitivity of thepatients to insulin did change, with an increased response to insulin as the renal function declined. Careful glucose monitoring and dose reductions of insulin, including HumalogMix75/25, may be necessary in patients with renal dysfunction.Hepatic Impairment — Some studies with human insulin have shown increased circulating levels of insulin in patients with hepatic failure. The effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of Humalog Mix75/25 has not been studied. However, in a study of 22 patients with type 2 diabetes, impaired hepatic function did not affect the subcutaneous absorption or general disposition of Humalog when compared with patients with no history of hepatic dysfunction. In that study, Humalog maintained its more rapid absorption and elimination when compared with Regular human insulin. Careful glucose monitoring and dose adjustments of insulin, including Humalog Mix75/25, may be necessary in patients with hepatic dysfunction.INDICATIONS AND USAGEHumalog Mix75/25, a mixture of 75% insulin lispro protamine suspension and 25% insulin lispro injection, (rDNA origin), is indicated in the treatment of patients with diabetes mellitus for the control of hyperglycemia. Humalog Mix75/25 has a more rapid onset of glucose-lowering activity compared with Humulin 70/30 while having a similar duration of action. This profile is achieved by combining the rapid onset of Humalog with the intermediate action of insulin lispro protamine suspension.CONTRAINDICATIONSHumalog Mix75/25 is contraindicated during episodes of hypoglycemia and in patients sensitive to insulin lispro or any of the excipients contained in the formulation.WARNINGSHumalog differs from Regular human insulin by its rapid onset of action as well as a shorter duration of activity. Therefore, the dose of Humalog Mix75/25 should be given within 15 minutes before a meal.Hypoglycemia is the most common adverse effect associated with the use of insulins, including Humalog Mix75/25. As with all insulins, the timing of hypoglycemia may differ among various insulin formulations. Glucose monitoring is recommended for all patients with diabetes.Any change of insulin should be made cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type (e.g., Regular, NPH, analog), species, or method of manufacture may result in the need for a change in dosage.PRECAUTIONSGeneralHypoglycemia and hypokalemia are among the potential clinical adverse effects associated with the use of all insulins. Because of differences in the action of Humalog Mix75/25 and other insulins, care should be taken in patients in whom such potential side effects might be clinically relevant (e.g., patients who are fasting, have autonomic neuropathy, or are using potassium-lowering drugs or patients taking drugs sensitive to serum potassium level). Lipodystrophy and hypersensitivity are among other potential clinical adverse effects associated with the use of all insulins.As with all insulin preparations, the time course of Humalog Mix75/25 action may vary in different individuals or at different times in the same individual and is dependent on site of injection, blood supply, temperature, and physical activity.Adjustment of dosage of any insulin may be necessary if patients change their physical activity or their usual meal plan. Insulin requirements may be altered during illness, emotional disturbances, or other stress.Hypoglycemia — As with all insulin preparations, hypoglycemic reactions may be associated with the administration of Humalog Mix75/25. Rapid changes in serum glucose concentrations may induce symptoms of hypoglycemia in persons with diabetes, regardless of the glucose value. Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as long duration of diabetes, diabetic nerve disease, use of medications such as beta-blockers, or intensified diabetes control.Renal Impairment — As with other insulins, the requirements for Humalog Mix75/25 may be reduced in patients with renal impairment.Hepatic Impairment — Although impaired hepatic function does not affect the absorption or disposition of Humalog, careful glucose monitoring and dose adjustments of insulin, including Humalog Mix75/25, may be necessary.Allergy — Local Allergy — As with any insulin therapy, patients may experience redness, swelling, or itching at the site of injection. These minor reactions usually resolve in a few days to a few weeks. In some instances, these reactions may be related to factors other than insulin, such as irritants in the skin cleansing agent or poor injection technique.Systemic Allergy — Less common, but potentially more serious, is generalized allergy to insulin, which may cause rash (including pruritus) over the whole body, shortness of breath, wheezing, reduction in blood pressure, rapid pulse, or sweating. Severe cases of generalized allergy, including anaphylactic reaction, may be life threatening. Localized reactions and generalized myalgias have been reported with the use of cresol as an injectable excipient. Antibody Production — In clinical trials, antibodies that cross-react with human insulin and insulin lispro were observed in both human insulin mixtures and insulin lispro mixtures treatment groups.Information for PatientsPatients should be informed of the potential risks and advantages of Humalog Mix75/25 and alternative therapies. Patients should not mix Humalog Mix75/25 with any other insulin. They should also be informed about the importance of proper insulin storage, injection technique, timing of dosage, adherence to meal planning, regular physical activity, regular blood glucose monitoring, periodic hemoglobin A1c testing, recognition and management of hypo- and hyperglycemia, and periodic assessment for diabetes complications.Patients should be advised to inform their physician if they are pregnant or intend to become pregnant.Refer patients to the Patient Information leaflet for information on normal appearance, timing of dosing (within 15 minutes before a meal), storing, and common adverse effects.For Patients Using Insulin Pen Delivery Devices: Before starting therapy, patients should read the Patient Information leaflet that accompanies the drug product and the User Manual that accompanies the delivery device and re-read them each time the prescription is renewed. Patients should be instructed on how to properly use the delivery device, prime the Pen to a stream of insulin, and properly dispose of needles. Patients should be advised not to share their Pens with others.Laboratory TestsAs with all insulins, the therapeutic response to Humalog Mix75/25 should be monitored by periodic blood glucose tests. Periodic measurement of hemoglobin A1c is recommended for the monitoring of long-term glycemic control.Drug InteractionsInsulin requirements may be increased by medications with hyperglycemic activity such as corticosteroids, isoniazid, certain lipid-lowering drugs (e.g., niacin), estrogens, oral contraceptives, phenothiazines, and thyroid replacement therapy.Insulin requirements may be decreased in the presence of drugs that increase insulin sensitivity or have hypoglycemic activity, such as oral antidiabetic agents, salicylates, sulfa antibiotics, certain antidepressants (monoamine oxidase inhibitors), angiotensin-converting-enzyme inhibitors, angiotensin II receptor blocking agents, beta-adrenergic blockers, inhibitors of pancreatic function (e.g., octreotide), and alcohol. Beta-adrenergic blockers may mask the symptoms of hypoglycemia in some patients.Carcinogenesis, Mutagenesis, Impairment of FertilityLong-term studies in animals have not been performed to evaluate the carcinogenic potential of Humalog, Humalog Mix75/25, or Humalog Mix50/50. Insulin lispro was not mutagenic in a battery of in vitro and in vivo genetic toxicity assays (bacterial mutation tests, unscheduled DNA synthesis, mouse lymphoma assay, chromosomal aberration tests, and a micronucleus test). There is no evidence from animal studies of impairment of fertility induced by insulin lispro. PregnancyTeratogenic Effects — Pregnancy Category B — Reproduction studies with insulin lispro have been performed in pregnant rats and rabbits at parenteral doses up to 4 and 0.3 times, respectively, the average human dose (40 units/day) based on body surface area. The results have revealed no evidence of impaired fertility or harm to the fetus due to insulin lispro. There are, however, no adequate and well-controlled studies with Humalog, Humalog Mix75/25, or Humalog Mix50/50 in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nursing MothersIt is unknown whether insulin lispro is excreted in significant amounts in human milk. Many drugs, including human insulin, are excreted in human milk. For this reason, caution should be exercised when Humalog Mix75/25 is administered to a nursing woman. Patients with diabetes who are lactating may require adjustments in Humalog Mix75/25 dose, meal plan, or both. Pediatric UseSafety and effectiveness of Humalog Mix75/25 in patients less than 18 years of age have not been established.Geriatric UseClinical studies of Humalog Mix75/25 did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient should take into consideration the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in this population.ADVERSE REACTIONSClinical studies comparing Humalog Mix75/25 with human insulin mixtures did not demonstrate a difference in frequency of adverse events between the two treatments.Adverse events commonly associated with human insulin therapy include the following:Body as a Whole — allergic reactions (see PRECAUTIONS).Skin and Appendages — injection site reaction, lipodystrophy, pruritus, rash.Other — hypoglycemia (see WARNINGS and PRECAUTIONS).OVERDOSAGEHypoglycemia may occur as a result of an excess of insulin relative to food intake, energy expenditure, or both. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise, may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneousglucagon or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. DOSAGE AND ADMINISTRATIONTable 1*: Summary of Pharmacodynamic Properties of Insulin Products (Pooled Cross-Study Comparison)Insulin Products Dose, U/kg Time of Peak Activity, Hours After Dosing Percent of Total Activity Occurring in the First 4 Hours Humalog 0.3 2.4 (0.8 - 4.3) 70% (49 - 89%) Humulin R 0.32 (0.26 - 0.37) 4.4 (4.0 - 5.5) 54% (38 - 65%) Humalog Mix75/25 0.3 2.6 (1.0 - 6.5) 35% (21 - 56%) Humulin 70/30 0.3 4.4 (1.5 - 16) 32% (14 - 60%) Humalog Mix50/50 0.3 2.3 (0.8 - 4.8) 45% (27 - 69%) Humulin 50/50 0.3 3.3 (2.0 - 5.5) 44% (21 - 60%) NPH 0.32 (0.27 - 0.40) 5.5 (3.5 - 9.5) 14% (3.0 - 48%) NPL component 0.3 5.8 (1.3 - 18.3) 22% (6.3 - 40%) * The information supplied in Table 1 indicates when peak insulin activity can be expected and the percent of the total insulin activity occurring during the first 4 hours. The information was derived from 3 separate glucose clamp studies in nondiabetic subjects. Values represent means, with ranges provided in parentheses.Humalog Mix75/25 is intended only for subcutaneous administration. Humalog Mix75/25 should not be administered intravenously. Dosage regimens of Humalog Mix75/25 will vary among patients and should be determined by the healthcare provider familiar with the patient’s metabolic needs, eating habits, and other lifestyle variables. Humalog has been shown to be equipotent to Regular human insulin on a molar basis. One unit of Humalog has the same glucose-lowering effect as one unit of Regular human insulin, but its effect is more rapid and of shorter duration. Humalog Mix75/25 has a similar glucose-lowering effect as compared with Humulin 70/30 on a unit for unit basis. The quicker glucose-lowering effect of Humalog is related to the more rapid absorption rate of insulin lispro from subcutaneous tissue.Humalog Mix75/25 starts lowering blood glucose more quickly than Regular human insulin, allowing for convenient dosing immediately before a meal (within 15 minutes). In contrast, mixtures containing Regular human insulin should be given 30 to 60 minutes before a meal. The rate of insulin absorption and consequently the onset of activity are known to be affected by the site of injection, exercise, and other variables. As with all insulin preparations, the time course of action of Humalog Mix75/25 may vary considerably in different individuals or within the same individual. Patients must be educated to use proper injection techniques.Humalog Mix75/25 should be inspected visually before use. Humalog Mix75/25 should be used only if it appears uniformly cloudy after mixing. Humalog Mix75/25 should not be used after its expiration date.HOW SUPPLIEDHumalog Mix75/25 [75% insulin lispro protamine suspension and 25% insulin lispro injection, (rDNA origin)] is available in the following package sizes: each presentation containing 100 units insulin lispro per mL (U-100).10 mL vials NDC 0002-7511-01 (VL-7511)5 x 3 mL prefilled insulin delivery devices (Pen) NDC 0002-8794-59 (HP-8794)5 x 3 mL prefilled insulin delivery devices (KwikPen™) NDC 0002-8797-59 (HP-8797)Storage — Humalog Mix75/25 should be stored in a refrigerator [2° to 8°C (36° to 46°F)], but not in the freezer. Do not use Humalog Mix75/25 if it has been frozen. Unrefrigerated [below 30°C (86°F)] vials must be used within 28 days or be discarded, even if they still contain Humalog Mix75/25. Unrefrigerated [below 30°C (86°F)] Pens, and KwikPens must be used within 10 days or be discarded, even if they still contain Humalog Mix75/25. Protect from direct heat and light. See table below:Not In-Use (Unopened) Room Temperature [Below 30°C (86°F)] Not In-Use (Unopened)RefrigeratedIn-Use (Opened) RoomTemperature [Below30°C (86°F)]10 mL Vial 28 days Until expiration date 28 days,refrigerated/roomtemperature.3 mL Pen and KwikPen (prefilled) 10 days Until expiration date 10 days. Do notrefrigerate.Literature revised March 16, 2009KwikPens manufactured byEli Lilly and Company, Indianapolis, IN 46285, USAPens manufactured byEli Lilly and Company, Indianapolis, IN 46285, USA orLilly France, F-67640 Fegersheim, FranceVials manufactured byEli Lilly and Company, Indianapolis, IN 46285, USA orLilly France, F-67640 Fegersheim, Francefor Eli Lilly and Company, Indianapolis, IN 46285, USACopyright © 2007, 2009, Eli Lilly and Company. All rights reserved.PV 5551 AMP PRINTED IN USA。

赖脯胰岛素混合注射液致变态反应1例承瑛; 刘秀英【期刊名称】《《护理研究》》【年(卷),期】2010(024)004【总页数】1页(P313-313)【作者】承瑛; 刘秀英【作者单位】266071 中国人民解放军第四〇一医院【正文语种】中文【中图分类】R473.5赖脯胰岛素混合注射液(优泌乐25R)为含有25%赖脯胰岛素(超短效胰岛素类似物)和 75%精蛋白锌赖脯胰岛素(NPL,中效胰岛素类似物)混悬预混剂,在糖尿病病人中应用越来越广泛。

2008年11月我科发现1例皮下注射赖脯胰岛素混合注射液发生变态反应。

现报告如下。

1 病例介绍病人,男,79岁,患2型糖尿病20余年,由于血糖控制欠佳,于2008年 11月入院。

院外长期口服降糖药物治疗,未应用任何胰岛素。

既往无药物过敏史。

入院后在控制饮食的基础上应用赖脯胰岛素混合注射液早16 U、晚10 U,餐时腹部皮下注射。

入院第3天18:00皮下注射胰岛素30 min后注射部位出现红肿、大量斑丘疹、瘙痒等症状,无心悸、呼吸困难,立即给予10%葡萄糖酸钙注射液静脉注射,症状逐渐缓解。

次日晨更换注射部位,于上臂注射后仍出现类似现象,改用普通胰岛素注射液皮下注射后未出现上述症状,考虑为赖脯胰岛素混合注射液过敏,停用,给予抗过敏治疗后病人上述症状消失,住院期间未再出现变态反应。

2 讨论赖脯胰岛素是一种短效胰岛素类似物,是将人胰岛素B链C末端第28位脯氨酸与第29位赖氨酸进行换位修饰,这种换位改变了B链末端的空间结构,导致二聚体自我聚和能力下降,易于解离而加快吸收,既不影响胰岛素生物活性,又具有皮下吸收快、达峰时间短的特点,临床应用较广。

胰岛素种类较多,其变态反应产生的机制目前尚不完全清楚,一般认为与胰岛素制剂中的污染物、杂质蛋白或个体差异有关[1,2]。

值得注意的是,该病人应用的是混合赖脯胰岛素,其中鱼精蛋白是引起变态反应的常见因素。

鱼精蛋白是一种富含精氨酸(67%)的多阳离子、强碱性多肽,能延缓皮下注射胰岛素的吸收,其毒性反应有快速给药反应型、变态反应型及致命肺血管收缩型[3]。