硫酸奈替米星葡萄糖注射液稳定性研究

目的考察硫酸奈替米星葡萄糖注射液的稳定性。方法利用光照和高温、加速试验、长期试验测定对硫酸奈替米星葡萄糖注射液稳定性的影响。结果硫酸奈替米星葡萄糖注射液对光稳定性好,对于热在40℃稳定性良好,60℃稳定性稍差,加速试验,溶液外观颜色加深,降解产物5-羟甲基糠醛在3个月时已经超过规定,硫酸奈替米星的含量有所下降。长期试验,在室温放置九个月,产品外观、pH值、颜色、澄明度等项目没有显著变化。结论硫酸奈替米星葡萄糖注射液对光稳定,对热稳定性稍差但符合标准,加速试验和长期试验结果均符合要求。贮存时应置于阴凉干燥处。     

硫酸奈替米星注射液细菌内毒素检测研究

硫酸奈替米星（ＮｅｔｉｌｍｉｃｉｎＳｕｌｆａｔｅ）注射液为我国卫生部部标准〔１〕所载品种。规定其热原检查采用中国药典家兔法，剂量为１００００ｕ／ｍｌ·１ｍｌ／ｋｇ。美国药典２３版已采用细菌内毒素检查法检测硫酸奈替米星注射液热原〔２〕。因此我们对采用细...     

头孢他啶对奈替米星体内药动学的影响

目的 考察头孢他啶对奈替米星在受试者体内药动学的影响,为临床合理用药提供依据. 方法 12例受试者在单剂量静脉滴注奈替米星（单用组）或奈替米星加头孢他啶（联用组）后,采用高效液相色谱 间接光度法测定不同时间点血清及尿液中奈替米星浓度,计算其药动学参数及尿药回收率. 结果 单用、合用头孢他啶后奈替米星的体内过程均符合二房室开放模型,其药动学参数单用组AUC_0-t,t_1/2β,CL与0～24 h尿药回收率分别为（52.93±5.58） mg•L^-1•h、（3.68±0.33） h、（4.49±0.53） L•h^-1与72.22%,联用组分别为（71.81±8.03 ）mg•L^-1•h、（5.06±0.57） h、（2.95±0.37） L•h^-1与59.20%. 两组比较差异有显著性. 结论 奈替米星与头孢他啶联用后,其消除过程减慢,连续应用可能导致药物体内蓄积,二者合用时应适当减少奈替米星的剂量.     

老年 COPD 患者奈替米星静脉滴注给药的药动学研究与临床效果分析

目的：研究老年慢性阻塞性肺部疾病（ COPD）患者奈替米星（ NTM）静脉滴注给药在下呼吸道的分布和药物动力学,并分析其临床疗效和不良反应。方法24例COPD患者分为A、B组,每组12例。2组NTM剂量分别为A组每天7=．0 mg／kg,B组给予5．0 mg／kg,静脉滴注。利用荧光偏振免疫方法,使用尿素替代肺泡液稀释内标,测定肺泡液、支气管分泌液和血清中的NTM浓度。结果 A组药物动力学参数表现为,血清中NTM最高浓度Cmax可达（26．73±4．96）mg／L,消除半衰期为3．95 h;肺泡液中最高浓度为（7．75±2．12）mg／L,是血清Cmax的30％,而支气管分泌液中药物的浓度与肺泡液浓度呈正相关（ r ＝0．6434, P ＜0．05）。采用静脉滴注给药方式,肺泡中的药物浓度比常见肺炎致病菌的MIC值高。连续给药7 d后,所有患者均未见神经、肝、肾毒性。结论静脉滴注给药方式,给药间隔时间长,且不会增加不良反应,更适用于临床上老年COPD患者的治疗。     

静滴硫酸奈替米星注射液引起药疹2例

例1,女,54岁,因肺部感染,于2000年5月30日入院,入院后给予硫酸奈替米星注射液(批号000101)0.3 g/d静滴,第4天出现散在淡红色丘疹,略高出皮肤,呈圆型,部分成片,压之退色,略痒感,疹间肤色正常,主要以颈部、胸部为主,精神正常.立即停药,用抗过敏药西替利嗪(赛特赞)1#/d、葡萄糖酸钙1 g,tid,及炉甘石洗剂外用.改用头孢曲松2.0 g/d静滴,3 d后,症状减轻,两星期后痊愈出院.     

硫酸奈替米星及注射液初步稳定性试验

硫酸奈替米星及注射液初步稳定性试验汪素岩（浙江省药品检验所杭州３１０００４）任姿（温州制药厂质检科）药品稳定性考察是评价药品质量的一个重要指标之一，是为新药确定有效期，贮存条件的主要依据。本文对自制硫酸奈替米星原料药及注射液在室温强光照射、高温度、高...     

硫酸奈替米星葡萄糖注射液的生产工艺研究

目的　探讨硫酸奈替米星葡萄糖注射液的制备工艺,确定生产工艺参数和最佳生产工艺路线,为氨基糖苷类抗生素药物生产提供依据。方法　采用正交试验的方法优化生产工艺,并用室温留样试验方法进行初步稳定性考察,选择最佳工艺参数。结果　确定该产品生产工艺为加入适量的稳定剂,10 5℃,30min灭菌。结论　用该方法制备的硫酸奈替米星葡萄糖注射液质量稳定,有效期为2年。该生产工艺设计合理,可作为产品生产工艺规程执行。     

硫酸奈替米星注射液变色问题探讨

本文探讨了引起硫酸奈替米星注射剂变色的因素。结果证明：硫酸奈替米星注射剂对兴稳定，对热下稳定，药液本身的pH值，安瓿氮气的充量及稳定剂用量配比（在处方允许范围内）对注射剂在贮存期内的变色影响很大。     

硫酸奈替米星注射液临床疗效及药效学研究

使用国产硫酸奈替米星注射液治疗呼吸系统和泌尿系统感染共63例．临床有效率为98．4％，细菌阴转率和细菌清除率均为98．3％，不良反应发生率为9．1％。同时用庆大霉素随机对照治疗泌尿系统感染35例，奈替米星的临床疗效和细菌学疗效明显优于庆大霉素（P＜0．05），但不良反应发生率两者之间无显著性差异（P＞0.05）。体外药敏试验结果表明奈替米星的药物敏感率大于阿米卡星和庆大霉素，77．3％庆大霉素耐药菌和92．9％环丙沙星耐药大肠杆菌对奈替米星敏感，国产奈替米星的体外抗菌活性与进口产品相同。     

国产奈替米星临床与实验室研究

采用国产奈替米星和阿米卡星随机对照治疗各种类型急性细菌性感染２０４例，奈替米星７７例与阿米卡星７６例作随机对照，开放试验５１例。治愈率和有效率分别为７５．３％，９６．１％；６７．１％、９３．４％、８６．３％，９４．１％（Ｐ〉０．１，Ｐ〉０．２５），细菌清除率分别为９０．７；８８．０％；９３．０％（Ｐ〉０．０５），不良反应发生率分别为５．１％、３．９％、３．９％（Ｐ〉０．５），试验组和对照组临床疗效     

硫酸奈替米星注射液中细菌内毒素检查的研究

目的:建立硫酸奈替米星注射液的细菌内毒素检查方法。方法:参照中国药典1995年版二部收载的细菌内毒素检查方法进行实验。结果:通过干扰实验证明可以稀释而达到排除干扰作用。用灵敏度为 0.25 Eu/ml的鲎试剂检查细菌内毒素的方法可行、有效。结论:可以用细菌内毒素检查法替代家兔法来控制硫酸奈替米星注射液的质量。     

The neuromuscular blocking activity of a new aminoglycoside antibiotic netilmicin sulphate (SCH 20569)

The neuromuscular blocking activity of netilmicin sulphate (Sch 20569), a new aminoglycoside antibiotic, was studied on the rat sciatic nerve-gastrocnemius muscle preparation. The i.v. administration of netilmicin caused a gradual fall, up to complete blockade, of the muscular contraction elicited by nerve stimulation. Conversely, the muscular response to direct stimulation was not affected. The response pattern was similar to that seen with known aminoglycoside antibiotics. The acute toxic effects (LD50 i.p. in mice) of netilmicin were antagonized by pretreatment with neostigmine; this latter partially prevented netilmicin-induced blockade, but was not able to reverse it. Calcium chloride was the only agent effective both to prevent and to reverse the neuromuscular blocking effects of netilmicin.     

Pharmacokinetics of a netilmicin loading dose on the first postnatal day in preterm neonates with very w gestational age

Objective Pharmacokinetic parameters are important for dose adjustment of aminoglycosides, but they are highly variable in neonates. In this study the pharmacokinetics of a netilmicin loading dose was investigated on the first postnatal day in preterm neonates with very low gestational age (GA).Methods In an open prospective study, 20 neonates with GA between 22.9 and 32.0 weeks and suspected postnatal bacterial infection received an intravenous loading dose of 5 mg/kg netilmicin over 1 h during the first postnatal day. Netilmicin serum concentrations were determined by an enzyme multiplied immunoassay.Results The systemic clearance of netilmicin normalized to body weight (BW) was not significantly different in three GA subgroups (0.59± 0.02 ml/min/kg for GA <24 weeks, 0.72±0.14 ml/min/kg for GA 24–27 weeks, and 0.62±0.19 ml/min/kg for GA 27–32 weeks, P=0.123). Similar results were also obtained for serum elimination half-time and for the distribution volume normalized to BW. Multiple regression analysis showed that systemic clearance and volume of distribution (both not normalized to BW) significantly correlated with BW (P<0.0001) but not with GA. In the entire group, 20% of peak concentrations were below the target of 6 mg/l, and 63% of trough concentrations were above the target of 2 mg/l.Conclusion In neonates with very low GA, the pharmacokinetic parameters of netilmicin determined after an intravenous loading dose were not dependent on GA when normalized to BW. A number of neonates did not reach targeted peak and trough netilmicin serum concentrations, suggesting that a higher loading dose and a prolonged dosing interval might enhance the effectiveness and safety of netilmicin in preterm neonates immediately after birth.     

奈替米星与4种止血药配伍的稳定性考察

目的：本文考察了奈替米星分别与酚磺乙胺，止血芳酸，肾上腺色腙和氨基己酸在０．９％氯化钠注射液中配伍的稳定性。方法：采用微生物法、紫外分光光度法等考察了奈替米星分别与酚磺乙胺，止血芳酸，肾上腺色腙和氨基己酸配伍前后的含量变化情况。结果：在室温条件下，０～６ｈ内其外观，ｐＨ值及含量均无明显变化。结论：在上述条件下，奈替米星与以上４种止血药配伍，各组分基本稳定     

奈替米星体液浓度测定的方法学研究

通过对国产硫酸奈替米星注射后人体血尿中药物浓度测定，建立了奈替米星体液浓度测定的微生物法，该方法的检测限为０．０３７５～０．０７５１μｇ，最低检测浓度为０．２５～０．５μｇ／ｍｌ，回收率为８８．８％±３．６３％～９８％±１４．４０％，重复性试验相对标准差为２．２２％～５．３４％；并对１０例健康受试者用药后血标本１００余份进行了微生物法测定和高压液相色谱法测定，对两种方法测定结果的比较发现：微生物法测定的血药浓度明显高于ＨＰＬＣ法（Ｐ＜０．０１），而ＨＰＬＣ法由于需复杂的样品预处理和特殊的色谱条件，测定的血药浓度较低，回收率仅７１．９８％～７６．９６％。不过，两种方法测定结果的相关性较好。本研究结果提示：微生物法测定奈替米星体液浓度简便、易操作、结果准确可信，适用于体液药物浓度测定。     

奈替米星的光度分析研究

奈替米星(NTM)与曲利本蓝(TB)在pH2.5~6.0的条件下反应生成具有正吸收和负吸收的蓝色离子缔合物,其最大吸收波长位于688nm,线性范围为0~8.6mg/L;最大褪色波长为592nm,线性范围为0~9.5mg/L;表观摩尔吸光系数(ε)为1.08×104(正吸收)L/(mol.cm)和3.26×104(负吸收)L/(mol.cm)。当用双波长叠加法时,ε值可达4.35×104L/(mol.cm)。本文探讨了适宜的反应条件及主要分析化学性质。该法操作简便,有较高的灵敏度和选择性,用于市售奈替米星药物中奈替米星含量的测定,结果满意。     

Shelf lives of aseptically prepared medicines--stability of netilmicin injection in polypropylene syringes

There is no published information on the stability of netilmicin solutions in prefilled syringes. The purpose of this study was to evaluate the stability of netilmicin in polypropylene syringes and to determine the optimum validated shelf life so that they may be prepared in bulk in appropriately licensed facilities.

The syringes containing netilmicin 10 or 100 mg/ml were stored at 7 °C, room temperature in the light (RTL) and 25 °C/60% relative humidity for up to 300 days.

Netilmicin concentration was determined by reversed phase high performance liquid chromatography (RP-HPLC) of the isoindole derivative formed with o-phthalaldehyde (OPA). The shelf lives were calculated using the maximum rate method applied to the netilmicin analytical data. At 7 °C 10 and 100 mg/ml solutions were stable for 90 days falling to 30 days at 25 °C and 60% RH. At RTL the 10 mg/ml solution was stable for 9 days.     

Individualising netilmicin dosing in neonates

Purpose  The aim of this study was develop an optimal dosing regimen for netilmicin in neonates. Methods  This was a population pharmacokinetic study in 97 neonates aged from 2 to 28 days after the due date who were being treated with netilmicin for suspected sepsis. The model was used to simulate dosing regimens. Results  The principle factors influencing netilmicin clearance (CL) were postmenstrual age (PMA) and current body weight (CWT), and the principal determinant of volume of distribution (V) was CWT. The final covariate model was CL = 0.192 × (CWT/2)^1.35 × (PMA/40)^1.03, V = 1.5 × (CWT/2)^0.3. The optimal dosing was 5 mg/kg ever 36 h, 5 mg/kg every 24 h, 6 mg/kg every 24 h and 7 mg/kg every 24 h for neonates ≤27, 28–30, 31–33 and ≥34 weeks PMA, respectively. Conclusion  Individualisation of netilmicin dosing in neonates requires adjustment of dose by body weight, and dosing interval by both PMA and CWT.     

Prediction of netilmicin disposition in neonates.

Multiple regression analyses of data from 33 neonates who received netilmicin therapy showed that concurrent treatment with other drugs (Drg), creatinine clearance (CLcr), gestational age (GA), and an apgar score of less than 6 at 1 min (Agl') were significant determinants of netilmicin clearance. Apparent volume of distribution was significantly affected by postnatal age (PNA), gender, the presence of ascites and/or oedema (A/O), and whether or not the neonate was small for gestational age (SGA). The following formulae were obtained: [formula: see text] The regression formulae were shown to predict netilmicin plasma concentrations with good precision and a non-significant bias in a further 15 neonates studied prospectively.