注射用灯盏花素Beagle犬和小鼠安全药理学差异性研究

目的观察注射用灯盏花素对Beagle犬呼吸系统、心血管系统以及ICR小鼠协调功能和自发活动的影响,考察药物可能关系到人安全性的非期望药理作用。方法 24只Beagle犬雌雄各半,按体重随机分为10、30、90 mg·kg-1和溶媒对照组,每组6只,平行测定动物给药前和给药后2 min、30 min、1 h、2 h及4 h的心电图、呼吸、血压及肛温;ICR小鼠80只雌雄各半,其中40只按体重随机分为10、100、500mg·kg-1和溶媒对照组,分别尾静脉给予不同剂量注射用灯盏花素后观察动物机体协调能力;另外40只同样分组测定给药后不同时间点的小鼠自发活动次数。结果相同时间点各剂量组与溶媒对照组及给药前自身比较发现,Beagle犬心电指标、体温、收缩压、舒张压和平均动脉压均有一定程度的波动,但差异无统计学意义(P>0.05)。ICR小鼠给药后高剂量组出现闭眼和运动减少等反应,1 h左右恢复正常;与溶媒对照组比较,各组动物协调功能差异没有统计学意义(P>0.05),高剂量组雌雄小鼠给药后2 min和30min自发活动次数均有下降的趋势,雌鼠给药后2 min自发活动次数明显减少(P<0.05)。结论在本实验条件下,单次静脉给予注射用灯盏花素对Beagle犬的呼吸、心血管系统及体温无明显影响。单次给予注射用灯盏花素对小鼠协调功能无明显影响,500 mg·kg-1注射用灯盏花素对雌性小鼠在2 min时会产生一过性的轻度躯体运动障碍或中枢抑制作用。     

紫杉醇脂质体在大鼠和荷瘤裸鼠体内的组织分布

目的：运用LC—MS／MS法测定紫杉醇脂质体在大鼠和荷瘤裸鼠体内的组织分布,比较注射用紫杉醇脂质体和紫杉醇注射液的体内分布特征。方法：大鼠分组后分别iv．7mg·kg-1受试和参比试剂,于给药前、给药后10min、1h、4h采集组织样品;荷瘤裸鼠分组后分别iv．10mg·kg-1受试和参比试剂,于给药前、给药后10min,1h,4h,8h采集组织样品,利用LC—Ms／Ms法对组织样品中药物含量进行测定。结果：大鼠iv．紫杉醇脂质体后10min在肝、心、肾、脑、子宫分布达到最大值．4h后各组织中药物含量均下降：荷瘤裸鼠iv．给药后10min在血、肝、脾、肺、肾、脂肪、睾丸分布量最大,8h后在脾、肠、肝、肿瘤中药物含量依然较高。结论：紫杉醇脂质体和紫杉醇注射液在大鼠和裸鼠体内的组织分布一致。静脉注射紫杉醇脂质体后．均能特异地分布到肝脏、肺和肠等。两制剂比较,紫杉醇脂质体具有更好的靶向性和更高的安全性。     

扁桃体切除围手术期预防性抗菌药物应用的临床研究

目的探讨慢性扁桃体炎手术治疗围手术期是否需要预防性使用抗菌药物。方法采用前瞻性研究,将确诊为慢性扁桃体炎,符合手术适应证的72例患者,按人院时间、半随机分为两组;A组,术前30min给予抗菌药物静脉点滴;B组,围手术期不使用任何抗菌药物。观察术后感染相关指标。结果两组术后疼痛高峰时间均出现在24h内,72h后疼痛基本消失;两组无一例术后继发性感染出血,而记录的术后72h体温,白细胞计数,白膜形成时间及白膜脱落时间,均差异无统计学意义（均P〉0．05）。结论慢性扁桃体炎手术治疗围手术期不需要预防性使用抗菌药物。     

马来酸桂哌齐特注射液致寒战高热一例

患者,男,42岁.因"高处坠落致伤头部并疼痛2h余"于2010年8月29日急诊入院.患者既往无药物过敏史.体格检查:体温36.5℃,脉搏85次/min,呼吸20次/min,血压125/80 mm Hg(1 mm Hg =0.133 kPa).头颅CT提示:双侧颞叶硬膜下血肿并脑挫裂伤,右顶硬膜外血肿,蛛网膜下腔出血,环池及基底池显影尚清晰,中线结构居中.诊断为"急性闭合性颅脑损伤、左下肢皮肤擦伤".予以止血、抗炎、神经营养(马来酸桂哌齐特注射液160mg+注射用氯化钾0.5g+葡萄糖氯化钠注射液250ml静脉滴注,1次/d)、能量支持及肌内注射破伤风抗毒素等治疗.护理上密切观察患者瞳孔神志、血压、脉搏等变化情况.患者一直无不适.9月7日调整剂量,予以马来酸桂哌齐特注射液240 mg+注射用氯化钾1.0g+葡萄糖氯化钠注射液500ml静脉滴注,1次/d,当日使用无不适.9月10日继续输液治疗,在静脉滴注马来酸桂哌齐特240 mg+注射用氯化钾1.0g+葡萄糖氯化钠注射液500 ml约30 min后,患者出现寒战、高热,测体温38.4℃,立即停药,并给予盐酸异丙嗪注射液25 mg肌内注射,2h后患者症状未见消退,予以新癀片2片口服解热,约1h后缓解,体温37℃;4 h后体温36.5℃,恢复正常.9月11日未再使用马来酸桂哌齐特,继续其他治疗,患者未再发生类似症状.由此认为本次寒战、高热系马来酸桂哌齐特所引起.     

静脉、腹腔给予羟喜树碱冻干粉针和脂质体在小鼠血液中的分布

目的 研究羟喜树碱(HCPT)冻干粉针及脂质体通过小鼠腹腔及静脉给药其血液中的分布.方法 昆明种小鼠108只随机分成4组:2组腹腔给予冻干粉针及脂质体；另2组静脉给药.给药后15,60,120 min取血,测定羟喜树碱浓度.结果 腹腔给药后在15,60 min的血药浓度,羟基喜树碱脂质体较注射用羟基喜树碱明显减少；而120 min较注射用羟基喜树碱明显增加(P＜0.05).静脉给药后在60,120 min的药物浓度,较15 min时2组均明显减少(P＜0.05)；而120 min时的药物浓度,脂质体较注射剂明显增加(P＜0.05).结论 静脉、腹腔给予冻干粉针及脂质体HCPT,药物在血液中迅速分布,很快被消除,符合其药动学特征.     

注射用头孢曲松钠治疗感染性心内膜炎致药物热1例

1例66岁男性患者因感染性心内膜炎使用注射用头孢曲松钠等抗感染治疗,在使用注射用头孢曲松钠第13天后出现体温正常后再发热,血培养、超声及CT检查未见感染未控制或新发感染依据,停用注射用头孢曲松钠后,患者体温恢复正常。注射用头孢曲松钠致药物热明确。     

载两性霉素B的PLA-PEG纳米粒在小鼠体内的分布

采用改良的相分离法制备载有两性霉素B（1）的聚乳酸-聚乙二醇纳米粒，HPLC法检测小鼠脑组织及其它脏器中的药物浓度。以1粉针剂和1脂质体为对照，评价纳米粒的脑靶向作用。在小鼠脑内1粉针剂组未能检测出药物，1脂质体组于3h后能测得微量药物，1纳米粒组小鼠给药30min后脑内浓度达33．5ng／g，12h达最高（160．4ng／g）。     

临床药师参与1例急性髓细胞白血病合并鼻脑型毛霉病患者的诊疗实践

目的 为急性髓细胞白血病合并鼻脑型毛霉病的诊疗提供参考。方法 临床药师参与1例急性髓细胞白血病合并鼻脑型毛霉病患者的诊疗过程。临床药师通过查阅文献,根据患者基础疾病、临床表现、用药史,发现其鼻脑型毛霉病可能性大,建议医师及时进行诊断性检查,并建议使用注射用两性霉素B脂质体200 mg,qd进行针对性治疗。在使用两性霉素B脂质体期间,临床药师对患者、医护人员进行了用药教育和指导,并通过每日药学查房对可能发生的不良反应进行监测。结果 患者体温恢复正常,感染得到控制,使用两性霉素B脂质体期间并未发生不能耐受的不良反应,且停药后6个月未见复发。结论 对于有鼻脑型毛霉病高危因素的患者,可根据其临床表现,结合既往抗感染药物使用史、实验室检查结果综合判断毛霉菌感染的风险;在进行诊断性检查的同时,可经验性使用针对性药物进行治疗,以降低病死率。毛霉菌感染的首选药物为两性霉素B脂质体,但长期、大剂量使用会增加患者不良反应发生风险,应及早采取措施干预并做好患者的用药教育,提高其依从性,保证用药剂量和疗程足够。     

紫杉醇脂质体预处理用药方案的安全性研究

目的:探讨上消化道肿瘤用紫杉醇脂质体化疗的几种预处理用药方案的安全性方法:紫杉醇脂质体联合其它化疗药物治疗上消化道肿瘤26例。用紫杉醇脂质体前30min予地塞米松10 mg,静脉注射(i);地塞米松5 mg,静脉注射(ii);甲强龙40 mg,静脉注射(iii);或用紫杉醇脂质体前12 h及2 h口服地塞米松6 mg(i)、4.5 mg(ii)、2.25 mg(iii)。结果:化疗毒副反应主要为Ⅰ～Ⅱ度白细胞减少、贫血、恶心和呕吐,经对症处理后好转。与预处理相关的不良反应包括失眠、血糖升高、乏力、眩晕,无过敏性休克或治疗相关死亡发生。结论:用紫杉醇脂质体前30min予甲强龙40 mg,静脉注射,或用紫杉醇脂质体前12 h及2 h口服地塞米松2.25 mg是较好的预处理用药方案     

静脉滴注磷霉素钠致药物热反应一例

<正>患者男,46岁,农民。因右侧膝关节韧带断裂入我院治疗。入院检查:体温37℃,脉搏95次/min,呼吸22次/min,血压130/70mmHg(1mmHg=0.133kPa);发育正常,营养中等;神志清,检查合作。做注射用青霉素皮试(+)。术后给予5%葡萄糖注射液+磷霉素钠注射液静脉滴注,约1h左右,患者出现寒战、高热。体温达39℃,脉搏82次/min分,呼吸20次/min,血压135/70mmHg,两侧肺部听诊无音。给予退热药物,但体温一直不退。停药后体温下降较快。次日当重新应用此药物时,发热又复出现。     

肝动脉注射阿霉素温度敏感脂质体的靶行为和治疗应用的研究

Temperature sensitive liposome entrapped adriamycin was injected into the hepatic artery of Wistar rats bearing implanted hepatic tumor. Two hours after the injection, the liver was heated to 42 ℃ and maintained at that temperature for 6 minutes using a local hyperthermia. The variation in the pattern of the concentration of the liposomal drug in circulation, and the drug distribution in tissues were investigated. Results indicated that adriamycin was released from the liposomes with the drug concentration peaking in circulation at 30 minutes after heating. Following the hyperthermia treatment, the total amount of drug in the liver decreased, while that in the tumor and urine increased. The ¹⁴C labeled liposome track test showed that a parallel relationship between the lipid and the drug was maintained for 8 hours after the hepatic injection, and physiological environment was a determinant of change and existence of liposomal carrier. However, the drug encapsulated in the liposomes can be controlled by hyperthermia to target the tumor. Therapeutic experiments showed that in the group treated with the hepatic artery- injected liposome plus hyperthermia control, the liver tumor growth of the rats administered at 7 days after W₂₅₆ carcinosarcoma implantation on liver was notably inhibited and the life-span of the animal was greatly extended compared with those of aqueous administration groups and ⅳ injected liposome group.     

多相脂质体139抑制DNA、RNA、蛋白质生物合成机制的初步研究

多相脂质体139能够明显抑制癌细胞 DNA 合成,其抑制~3H—TdR 掺入艾氏腹水癌细咆 DNA 合成的曲线为缓慢递增型,表现为可逆性抑制并具有浓度依赖性。药物剂量为1.0mg/ml 时对 RNA 合成呈现轻度抑制并导致癌细胞核酸含量减少。“139”对S—180鼠肿瘤细胞蛋白质合成作用显著,最高抑制率为67.8%。对 RRL 蛋白质合成抑制率为46.8%,这种抑制作用是在延迟了十分钟后表现出来的,说明反应体系中聚核糖核蛋白体上已经开始合成肽链的核糖核蛋白体仍可继续完成肽链的合成,而新的核糖核蛋白体重新由其亚基组合时则受到一定抑制。“139”对肽酰—~3H—嘌吟霉素结合反应并无抑制作用,故不是转肽抑制剂.     

延胡索的药理研究 Ⅶ.延胡索乙素对狗胃液分泌的影响及其催眠作用

1.实验用具有Thomas改良式小胃狗3只,其中2只单次皮下注射乙素20毫克/公斤后,对胃液分泌量没有显著影响。皮下注射40毫克/公斤连续12天,胃液分泌总量无显著变化,仅在给药的个别天数的第1小时的胃液分泌略有减少,对胃液酸度及消化力的影响也不明显。另1只狗单次皮下注射80毫克/公斤,在前后2次试验中,4小时胃液分泌总量都受到显著抑制,其中以第1、第2、第3小时减少最明显,胃液酸度(游离酸、总酸)及消化力也有明显减弱现象。2.狗2只每天皮下注射乙素40毫克/公斤,共12天。于给药后5—20分钟出现催眠作用,催眠时间持续在80分钟左右。在给药几次以后有消减现象,以后又有回升,至第11、第12天时,动物的催眠作用再度出现减弱,有一定的耐受现象。3.单次皮下注射乙素20及80毫克/公斤或是40毫克/公斤多次给药,对上述3只狗的呼吸都没有明显影响。     

Sorption of amiodarone to polyvinyl chloride infusion bags and administration sets

The loss of amiodarone from i.v. admixtures to flexible polyvinyl chloride (PVC) infusion bags and i.v. administration sets was studied. Admixtures containing amiodarone hydrochloride 600 micrograms/mL and either 5% dextrose injection or 0.9% sodium chloride injection were stored at room temperature in glass bottles (both with and without contact of the drug solution with the rubber bottle closure), in flexible PVC bags, or in rigid PVC bottles. After 120 hours, the contents of each flexible PVC bag were emptied and replaced by methanol, which was allowed to remain in the bag for an additional 120 hours and was then analyzed for amiodarone content. To determine availability of amiodarone after infusion through a 1.8-m PVC i.v. administration set, solutions stored in glass containers were run through the set at 0.5 mL/min for 90 minutes. Samples of drug solutions were collected at appropriate intervals and analyzed by a stability-indicating high-performance liquid chromatography (HPLC) assay. Admixtures containing 0.9% sodium chloride injection were not stable; visual incompatibility was evident after 24 hours of storage in glass bottles, and no further testing was performed. In admixtures containing 5% dextrose injection that were stored in 50-mL flexible PVC bags, 60% of the initial amiodarone concentration remained after 120 hours; approximately half of the lost drug was recovered with the methanol. In effluent collected from the PVC administration set, 82% of the initial amiodarone concentration remained. Amiodarone concentrations did not decrease appreciably, after storage in glass or rigid PVC bottles, indicating that drug loss was probably affected by the plasticizer, di-2-ethylhexyl phthalate.(ABSTRACT TRUNCATED AT 250 WORDS)     

静脉滴注赖氨匹林治疗发热患者的疗效观察

目的比较静脉滴注赖氨匹林与复方氨林巴比妥注射液、对乙酰氨基酚片对发热患者的退热疗效。方法选择发热患者120例,随机分成三组,每组40例。A组给予赖氨匹林注射剂0.9g加入0.9%生理盐水100ml静脉滴注;B组给予复方氨林巴比妥注射液（安痛定）2ml肌肉注射;C组给予对乙酰氨基酚片0.5g口服。三组病例用药30min,60min,120min各测体温1次,观察退热疗效。结果赖氨匹林组退热效果最快,用药30min,体温降至（38.5±0.2）℃,总有效率82.5%;用药60min体温降至（37.7±0.3）℃,总有效率90%;用药120min体温降至（36.6±0.4）℃,总有效率95%。在相同条件下,赖氨匹林的退热疗效高于复方氨林巴比妥和对乙酰氨基酚。结论静脉滴注赖氨匹林退热效果快,不良反应小,是理想、安全的退热药物,值得临床推广。     

美罗培南透过血脑屏障的观察分析

目的 验证开颅手术前静脉注射美罗培南预防颅内感染的有效性.方法选择21~64岁的开颅手术患者,开颅手术前留置腰大池引流管,术前30min静脉给予美罗培南1.0g,给药的起始时间记为0点,采集静脉血和脑脊液标本时间为给药后0.5、1、2、3、4h,采用高效液相色谱法(HPLC)检测美罗培南浓度.结果血清峰浓度为(52.88±4.39)mg/L,达峰时间为30min.脑脊液峰浓度为(2.85±0.19)mg/L,达峰时间为2h.美罗培南术前静脉持续注射时脑脊液最大穿透率为13.75%±7.26%,最大穿透率出现的时间为静点后3h.结论 术前30min经静脉注射抗生素美罗培南,脑脊液中药物浓度在注射后2h达到最大值并可持续数小时.经静脉注射1.0g美罗培南,血清稳态药物浓度高于多数颅内感染常见致病菌的MIC90.     

Fundamental and clinical studies on CS--1170 in pediatric field (author's transl)]

Fundamental studies and clinical evaluation of CS-1170 were carried out in the field of pediatrics, and the following results were obtained: 1) A high serum concentration of the drug was observed by 30 minutes after the commencement of intravenous drip infusion of 20 and 30 mg/kg, with the peak appearing at the end of the infusion. Serum level of 10.0 micrograms/ml or more was observed even 2 hours after the completion of the drip infusion. 2) The peak of serum concentration appeared at 30 minutes after intravenous injection of 20 mg/kg, and the blood level 4 hours after the injection was 4.3 micrograms/ml or more. 3) Excretion of the drug into the urine by 6 hours after intravenous drip infusion or one-shot injection was 60% or more on the average, with the major portion of the drug in the active state excreted by 4 hours after the administration. 4) Twenty-five children with acute infections (5 types of diseases) were treated with CS-1170 mainly by intravenous drip infusion, and the following clinical results were obtained: The overall clinical effective rate of 96.0% was obtained with the daily dosage of CS-1170 ranging mostly from 50 to 80 mg/kg in the total 25 cases including 7 cases of acute bronchitis (100%), 13 cases of bronchopneumonia (92.3%), 3 cases of acute urinary tract infections (100%), a case each of staphylococal exanthema and lymphadenitis in the neck (100%). 5) Thorough analyses of the liver and kidney functions and the hematological features at the time of, and about 10 days after the administration of CS-1170 in each case so far revealed no abnormality. The drug did not affect the site of injection or the whole body.     

喜炎平注射液与3种注射剂的配伍稳定性研究

目的研究室温6h内喜炎平注射液在5%葡萄糖注射液中与注射用地塞米松磷酸钠、注射用维生素B6及10%氯化钾注射液的配伍稳定性,为临床合理用药提供科学依据。方法采用高效液相色谱法测定喜炎平注射液在5%葡萄糖注射液中与3种注射剂配伍后6h内喜炎平的含量,观察配伍后喜炎平含量、6h内溶液的外观及pH值的变化情况。结果在室温条件下,喜炎平注射液在5%葡萄糖注射液中与上述3种注射剂配伍6h内外观均无明显变化;喜炎平注射液与注射用维生素B6配伍后含量有所下降,但3h内基本稳定,pH略有下降;喜炎平注射液与注射用地塞米松磷酸钠配伍后含量略有上升,但总体变化不大,pH略有上升;喜炎平注射液与氯化钾注射液配伍后含量、pH都变化不大。结论在室温条件下,喜炎平注射液在5%葡萄糖注射液中与上述3种注射剂在6h内配伍基本稳定,但与维生素B配伍需谨慎。     

米索前列醇合并盐酸丁卡因胶浆用于人工流产术中临床效果观察

目的：探讨人工流产术前松弛宫颈的最好的用药方法,减轻疼痛程度,减少药物副反应。方法：选择600例自愿要求行人工流产手术、无手术禁忌的早孕妇女、年龄在20～40岁,随机分成A、B、C三组,A组于人工流产术前1h舌下含服米索前列醇100μg,吸宫前2min于宫颈管内注入盐酸丁卡因胶浆1支;B组于术前4h口服米索前列醇400μg;C组于术前4h阴道后穹隆放置米索前列醇400μg,放置后平卧30min。结果：三组对比宫颈松弛度、术中镇痛效果差异无统计学意义,P〉0.05,但A组扩张宫颈显效率、无痛率明显高于B、C两组,差异有统计学意义,P〈0.005。A组用药后药物副反应明显低于B、C两组,差异有统计学意义,P〈0.005。结论：小剂量米索前列醇联合丁卡因胶浆用于人工流产术前宫颈松弛度高、镇痛效果好,副反应明显减少,适合在基层使用。