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2-[(4R,5S,6S,7R,9R,10R,11E,13E,16S)-6-[(2S,3R,4R,5S,6R)-5-[(2R,4S,5R,6R)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-10-[(2R,5S,6S)-5-(dimethylamino)-6-methyloxan-2-yl]oxy-4-hydroxy-5-methoxy-9,16-dimethyl-2-oxo-1-oxacyclohexadeca-11,13-dien-7-yl]acetaldehyde | 8025-81-8

中文名称
——
中文别名
——
英文名称
2-[(4R,5S,6S,7R,9R,10R,11E,13E,16S)-6-[(2S,3R,4R,5S,6R)-5-[(2R,4S,5R,6R)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-10-[(2R,5S,6S)-5-(dimethylamino)-6-methyloxan-2-yl]oxy-4-hydroxy-5-methoxy-9,16-dimethyl-2-oxo-1-oxacyclohexadeca-11,13-dien-7-yl]acetaldehyde
英文别名
——
2-[(4R,5S,6S,7R,9R,10R,11E,13E,16S)-6-[(2S,3R,4R,5S,6R)-5-[(2R,4S,5R,6R)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-10-[(2R,5S,6S)-5-(dimethylamino)-6-methyloxan-2-yl]oxy-4-hydroxy-5-methoxy-9,16-dimethyl-2-oxo-1-oxacyclohexadeca-11,13-dien-7-yl]acetaldehyde化学式
CAS
8025-81-8
化学式
C43H74N2O14
mdl
——
分子量
843.1
InChiKey
ACTOXUHEUCPTEW-IMDCDJEBSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

物化性质

  • 熔点:
    126-128 °C
  • 沸点:
    914℃
  • 比旋光度:
    D20 -80° (methanol)
  • 闪点:
    >110°(230°F)
  • 溶解度:
    乙醇:50 mg/mL,清澈至微浑浊,淡黄色
  • 颜色/状态:
    Amorphous
  • 蒸汽压力:
    9.9X10-31 mm Hg at 25 °C (est)
  • 亨利常数:
    Henry's Law constant = 9.0X10-35 atm-cu m/mol at 25 °C (est)
  • 旋光度:
    Specific optical rotation: -80 deg at 20 °C/D
  • 分解:
    When heated to decomposition it emits acrid smoke & irritating fumes.
  • 解离常数:
    pKa1 = 7.88; pKa2 = 9.28 (est)

计算性质

  • 辛醇/水分配系数(LogP):
    2.1
  • 重原子数:
    59
  • 可旋转键数:
    11
  • 环数:
    4.0
  • sp3杂化的碳原子比例:
    0.86
  • 拓扑面积:
    195
  • 氢给体数:
    4
  • 氢受体数:
    16

ADMET

代谢
在牛中,形成了新斯皮拉霉素这种代谢物,它是脱糖基衍生物。在给药后14-28天,肌肉和肾脏中新斯皮拉霉素的浓度略高于螺旋霉素;在肌肉中,新斯皮拉霉素和螺旋霉素的水平大约相等。
In cattle, the metabolite neospiramycin, the demycarosyl derivative, is formed. Concentrations of neospiramycin in muscle and kidney were marginally higher than those of spiramycin 14-28 days after dosing; in muscle, levels of neospiramycin and spiramycin were approximately equal.
来源:Hazardous Substances Data Bank (HSDB)
代谢
spiramycin在肝脏中被代谢成活性代谢物;大量通过胆汁排出,约10%通过尿液排出。
Spiramycin is metabolized in the liver to active metabolites; substantial amounts are excreted in the bile and about 10% in the urine.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 毒性总结
识别和使用:螺旋霉素是一种大环内酯类抗生素,用于治疗和控制动物中多种细菌和支原体感染。它以螺旋霉素磷酸盐的形式用于动物饲料,并作为更易溶的螺旋霉素酯形式通过其他途径给药。它还被用于治疗原虫感染,如隐孢子虫病和弓形虫病。人类暴露和毒性:据报道,螺旋霉素在职业环境中会引起接触性皮炎。一名在饲料厂工作的男子由于空气中的螺旋霉素而患上了过敏性接触性皮炎。患者在工作期间裸露区域出现反复的湿疹病变。螺旋霉素还据报道会引起过敏反应。一名34岁的女性在制药厂处理螺旋霉素粉末时出现了鼻炎和刺激性咳嗽。接触药物后几小时内出现症状,并在离开工作场所后持续数小时。一名35岁的非过敏性维护工程师在制药行业工作一年后出现了打喷嚏、咳嗽和呼吸困难的发作。在医院进行的逐渐增加螺旋霉素剂量的吸入挑战测试重现了他的症状,并导致了迟发型哮喘反应的发生。此外,还报告了两例制药厂工人因螺旋霉素引起的支气管哮喘。受试者在接触螺旋霉素粉末时在工作时出现咳嗽、呼吸困难和哮喘症状。离开工作3或4天后症状消失。动物研究:每组2只雄性和2只雌性猴子(Macaca fascicularis)每天静脉注射0、240,000、360,000和540,000 IU/kg bw的螺旋霉素酯,持续5天。所有剂量组在注射期间都出现过度流涎。在几只高剂量猴子和一只低剂量猴子中出现肌肉张力减退和恶心性痉挛。体重没有异常,但所有处理动物的食物消耗量都减少了。在高剂量动物中注意到血红蛋白、红细胞数量和血细胞比容略有下降。在大鼠进行的短期饮食研究中,给予相当于最高3900 mg/kg bw的剂量,持续13周,注意到的唯一主要效果是一些中剂量和高剂量动物的中性粒细胞计数减少,以及盲肠扩张。在另一项大鼠饮食研究中,动物被给予相当于最高720 mg/kg bw/day的剂量,持续一年。注意到的唯一显著效果是高剂量雌性动物的体重减轻,以及高剂量水平下两性动物的相对肝、肾和肾上腺重量增加。在所有剂量水平下都发生了肝糖原耗竭,但对照组没有。在给予杂种犬500 mg/kg bw/day,持续最多56天的实验中,观察到精子生成减少和睾丸萎缩。还看到了肾脏损伤。当比格犬口服相当于最高150 mg/kg bw/day的螺旋霉素,持续两年时,没有看到睾丸损伤,尽管其他器官发生了退行性变化。在针对小鼠的致畸性研究中,妊娠第5-15天口服螺旋霉素400 mg/kg bw对妊娠结果没有影响。大鼠妊娠第6-15天和兔妊娠第6-19天静脉注射最高84 mg/kg bw/day的剂量对发育没有影响,但在兔口服200和400 mg/kg bw/day的剂量时,母体产生了盲肠扩张。在妊娠第6-15天,20只怀孕大鼠被静脉注射0、90,000、180,000和270,000 IU/kg bw/day的螺旋霉素酯。最高剂量给药后立即产生短暂的(5分钟)共济失调和震颤。中间剂量下胎儿体重略有但显著下降,但所有值都在历史对照范围内。在此研究中没有注意到任何胎儿异常增加。在一项研究中,雄性大鼠通过未指明的途径给予30 mg/kg bw/day的剂量,持续8天,注意到了精原细胞的有丝分裂和减数分裂异常。在体外哺乳动物细胞正向突变试验、体外细胞遗传学分析和小鼠微核试验中,螺旋霉素酯和螺旋霉素磷酸盐均得到了阴性结果。
IDENTIFICATION AND USE: Spiramycin is a macrolide antibiotic used for the treatment and control of a number of bacterial and mycoplasmal infections in animals. It is available as a spiramycin embonate for use in animal feed, and as the adipate, a more soluble form, for administration by other routes. It has also been used in the protozoal infections cryptosporidiosis and toxoplasmosis. HUMAN EXPOSURE AND TOXICITY: Spiramycin is reported to cause contact dermatitis in occupational settings. A man who worked in a feed factory developed allergic contact dermatitis due to airborne spiramycin. The patient suffered recurrent outbreaks of eczematous lesions on uncovered areas during working periods. Spiramycin is also reported to cause hypersensitivity reactions. Rhinoconjunctivitis and spasmodic cough are reported in a 34 year-old female handling spiramycin powder in a pharmaceutical factory. The symptoms appeared within the first few hours of coming into contact with the drug and continued for several hours after leaving her place of work. One year after starting work in the pharmaceutical industry a 35-year-old non-atopic maintenance engineer developed attacks of sneezing, coughing and breathlessness. Inhalation challenge tests carried out in the hospital with gradually increasing quantities of spiramycin reproduced his symptoms and led to the development of late asthmatic reactions. Additionally, two cases of bronchial asthma due to spiramycin in workers of a pharmaceutical factory were reported. The subjects complained of cough, breathlessness and symptoms of asthma at work when coming into contact with spiramycin's powder. The symptoms cleared when away from work for more than 3 or 4 days. ANIMAL STUDIES: Groups of 2 male and 2 female monkeys (Macaca fascicularis) were given daily intravenous injections of 0, 240,000, 360,000, and 540,000 iu/kg bw/day spiramycin adipate for 5 days. Hypersalivation occurred during injection in all dose groups. Muscle hypotonia and nauseous spasticity occurred in several high dose monkeys and in one given the low dose. No abnormalities of body weights occurred but food consumption was reduced in all treated animals. A slight decrease in hemoglobin, red cell numbers and hematocrit was noted in high dose animals. In a short-term dietary study in which rats were given the equivalent of up to 3900 mg/kg bw for 13 weeks, the only major effects noted were a reduction in neutrophil counts in some mid- and high-dose animals, and the dilatation of the caecum. In another dietary study in the rat, animals were given up to the equivalent of 720 mg/kg bw/day for one year. The only notable effects were reductions in the body weights of females receiving the high doses, and increases in relative liver, kidney, and adrenal weights at high dose levels in animals of both sexes. Hepatic glycogen depletion occurred at all dose levels but not in controls. In mongrel dogs given 500 mg/kg bw/day for up to 56 days, reductions in spermatogenesis and testicular atrophy occurred. Kidney damage was also seen. When beagles were given orally spiramycin at up to the equivalent of 150 mg/kg bw/day for two years, testicular damage was not seen although degenerative changes occurred in other organs. In teratogenicity studies in mice, oral doses of spiramycin of up to 400 mg/kg bw given over days 5-15 of gestation had no effects on the outcome of pregnancy. intravenous doses of up to 84 mg/kg bw/day given on days 6-15 of gestation to rats and day 6-19 to rabbits had no effect on developmental, but oral dose of 200 and 400 mg/kg bw/day in rabbit produced caecal enlargement in mothers. Groups of 20 pregnant rats were treated intravenously on days 6-15 of gestation with doses of 0, 90 000, 180 000, and 270 000 iu/kg bw/day with spiramycin adipate. The highest dose given produced brief (5 minutes) ataxia and tremors immediately after dosing. A slight but significant reduction in fetal weight occurred at the intermediate dose but all values were within historical control ranges. There were no increased incidences of any fetal anomaly noted in this study. In a study where male rats were given doses of 30 mg/kg bw/day for 8 days by an unspecified route, mitotic and meiotic abnormalities in spermatogonia were noted. Negative result were obtained with spiramycin adipate and embonate in a forward-mutation test in mammalian cells in vitro, in an in vitro cytogenic assay, and in the mouse micronucleus test.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 相互作用
大环内酯类抗生素包括天然成员、前药和半合成衍生物。这些药物适用于多种感染,并且常常与其他药物疗法联合使用,因此存在潜在的药代动力学相互作用。大环内酯类可以通过在肝脏形成复合物并使微粒体药物氧化酶失活来抑制药物代谢,同时通过其抗生素效果干扰肠内微生物群。在过去的20年中,有多份报告指出大环内酯类是临床严重药物相互作用的潜在来源。然而,不同的大环内酯类在这方面存在差异,并非所有的大环内酯类都会引起药物相互作用。随着许多半合成大环内酯类抗生素的近期出现,现在很明显,它们可能被分为三类,以引起药物相互作用。第一组(例如酮内酯、红霉素)是那些容易形成亚硝基烷的药物,并因此形成不活跃的细胞色素P450-代谢物复合物。第二组(例如交沙霉素、氟红霉素、罗红霉素、克拉霉素、米卡霉素和米地卡霉素)形成复合物的程度较小,很少产生药物相互作用。最后一组(例如螺旋霉素、罗吉卡霉素、地红霉素和阿奇霉素)不会使细胞色素P450失活,也无法改变其他化合物的药代动力学。似乎有两个结构因素对于大环内酯类抗生素导致细胞色素P450的诱导以及在体内或体外形成抑制性的细胞色素P450-铁-亚硝基烷代谢物复合物非常重要:大环内酯分子中存在一个非阻碍性的、易于接近的N-二甲氨基团以及药物的疏水性。酮内酯是微粒体肝酶的最强抑制剂,能显著减少甲基强的松龙、茶碱、卡马西平、非那宗(安替比林)和三唑仑的代谢。酮内酯可以在接受麦角生物碱的患者中引起麦角中毒,在服用口服避孕药的患者中引起胆汁淤积性黄疸。红霉素及其不同的前药似乎是对药物代谢的较不强的抑制剂。然而,案例报告和控制研究已经表明,红霉素可能会与茶碱、卡马西平、甲基强的松龙、华法林、环孢素、三唑仑、咪达唑仑、阿芬太尼、双异丙吡胺和溴隐亭相互作用,减少药物清除。在接受大量还原型地高辛代谢物排泄的患者中,红霉素似乎也能增加地高辛的生物利用度,这可能是由于破坏了负责形成这些化合物的肠内微生物群。这些被指责的大环内酯类抗生素不应与其他已知会受到它们代谢影响的药物同时使用,或者至少,联合使用应仅在仔细监测患者的情况下进行。
The macrolide antibiotics include natural members, prodrugs & semisynthetic derivatives. These drugs are indicated in a variety of infections & are often combined with other drug therapies, thus creating the potential for pharmacokinetic interactions. Macrolides can both inhibit drug metab in the liver by complex formation & inactivation of microsomal drug oxidising enzymes & also interfere with microorganisms of the enteric flora through their antibiotic effects. Over the past 20 yrs, a number of reports have incriminated macrolides as a potential source of clinically severe drug interactions. However, differences have been found between the various macrolides in this regard & not all macrolides are responsible for drug interactions. With the recent advent of many semisynthetic macrolide antibiotics it is now evident that they may be classified into 3 different groups in causing drug interactions. The first group (e.g. troleandomycin, erythromycins) are those prone to forming nitrosoalkanes & the consequent formation of inactive cytochrome P450-metabolite complexes. The second group (e.g. josamycin, flurithromycin, roxithromycin, clarithromycin, miocamycin & midecamycin) form complexes to a lesser extent & rarely produce drug interactions. The last group (e.g. spiramycin, rokitamycin, dirithromycin & azithromycin) do not inactivate cytochrome P450 & are unable to modify the pharmacokinetics of other cmpds. It appears that 2 structural factors are important for a macrolide antibiotic to lead to the induction of cytochrome P450 & the formation in vivo or in vitro of an inhibitory cytochrome P450-iron-nitrosoalkane metabolite complex: the presence in the macrolide molecules of a non-hindered readily accessible N-dimethylamino group & the hydrophobic character of the drug. Troleandomycin ranks first as a potent inhibitor of microsomal liver enzymes, causing a significant decr of the metab of methylprednisolone, theophylline, carbamazepine, phenazone (antipyrine) & triazolam. Troleandomycin can cause ergotism in patients receiving ergot alkaloids & cholestatic jaundice in those taking oral contraceptives. Erythromycin & its different prodrugs appear to be less potent inhibitors of drug metab. Case reports & controlled studies have, however, shown that erythromycins may interact with theophylline, carbamazepine, methylprednisolone, warfarin, cyclosporin, triazolam, midazolam, alfentanil, disopyramide & bromocriptine, decreasing drug clearance. The bioavailability of digoxin appears also to be increased by erythromycin in patients excreting high amounts of reduced digoxin metabolites, probably due to destruction of enteric flora responsible for the formation of these cmpds. These incriminated macrolide antibiotics should not be administered concomitantly with other drugs known to be affected metabolically by them, or at the very least, combined admin should be carried out only with careful patient monitoring.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 相互作用
已报告在给予螺旋霉素时,左旋多巴的血浆浓度降低。
Reduced plasma concentrations of levodopa have been reported when given with spiramycin.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 相互作用
作者报告了一位21岁女性的病例,她患有先天性长QT综合症,经历了多次晕厥发作,至少有一次是由扭转性室性心动过速引起的。这种突然的并发症归因于48小时内同时开具了螺旋霉素和美喹他嗪。尽管这两种药物属于可能触发这种心律失常的药物家族,但它们并不被认为是扭转性室性心动过速的易感因素。撤除这种治疗导致晕厥发作完全消退,随访两年,最初的QTc间期显著缩短,尽管仍然比正常时间长。这个病例强调了这两种药物家族联合用药的潜在风险,尤其是在患有先天性长QT综合症的患者中。
The authors report the case of a 21 year old woman with a congenital long QT syndrome who had several syncopal attacks at least one of which was caused by torsades de pointes. This sudden complication was attributed to the simultaneous prescription of Spiramycine and Mequitazine over a 48 hour period. These two drugs are not considered to be predisposing factors for torsades de pointes despite the fact that they belong to two families of drugs which can trigger this type of arrhythmia. The withdrawal of this treatment led to the complete regression of the syncopal episodes with a follow-up of two years and a significant shortening of the initial QTc interval which remained, nevertheless, longer than normal. This case underlines the potential risks of drug associations of these two families of drugs, especially in patients with the congenital long QT syndrome.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 解毒与急救
/SRP:/ 立即急救:确保已经进行了充分的中和。如果患者停止呼吸,请开始人工呼吸,最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩,按训练操作。如有必要,执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐,让患者向前倾或将其置于左侧(如果可能的话,头部向下),以保持呼吸道畅通,防止吸入。保持患者安静,维持正常体温。寻求医疗帮助。 /毒物A和B/
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
spiramycin在口服给药后人体的吸收情况良好。健康青年男性成年人按15-30mg/kg体重口服给药后,在3-4小时内达到血浆峰浓度,血浆浓度为0.96-1.65mg/l。静脉给药(7.25mg/kg体重)后观察到较大的分布容积(Vdss 5.6 l/kg),表明组织分布广泛。生物转化似乎并不重要。胆汁排泄是主要的排泄途径;只有7-20%的口服剂量通过尿液排泄。已知spiramycin在肺和前列腺组织以及皮肤中达到较高的组织:血清浓度。
Spiramycin is well absorbed in humans after oral administration. Oral administration of 15-30 mg/kg bw to healthy young male adults resulted in peak plasma levels in 3-4 hours and plasma concentrations of 0.96-1.65 mg/l. After intravenous dosing (7.25 mg/kg b.w.) a large volume of distribution (Vdss 5.6 l/kg) was observed indicating extensive tissue distribution. Biotransformation did not appear to be important. Biliary excretion was the main route of excretion; only 7-20% of an oral dose was excreted in the urine. Spiramycin is known to achieve high tissue:serum concentrations in pulmonary and prostatic tissues, and in skin.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
spiramycin spiramycin穿过胎盘到达胎儿。母体血清、脐血和胎盘在每日2克用药方案后的抗生素浓度分别为1.19微克/毫升、0.63微克/毫升和2.75微克/毫升。当母体剂量增加到每日3克时,水平分别为1.69微克/毫升。分别0.78微克/毫升和6.2微克/毫升。根据这些结果,脐血:母体血清比约为0.5。此外,在这些剂量下,螺旋霉素在胎盘中的浓度约为母体血清的2-4倍。…螺旋霉素分泌入乳汁。接受1.5克/天治疗3天的哺乳期母亲的婴儿血清浓度为20微克/毫升。这种浓度具有抑菌作用。
Spiramycin crosses the placenta to the fetus. Concns of the antibiotic in maternal serum, cord blood, & the placenta after a dosage regimen of 2 g/day were 1.19 ug/ml, 0.63 ug/ml, & 2.75 ug/ml, respectively. When the maternal dose was increased to 3 g/day, the levels were 1.69 ug/ml, 0.78 ug/ml, & 6.2 ug/ml, respectively. Based on these results, the cord:maternal serum ratio is approx 0.5. Moreover, at these doses, spiramycin is concentrated in the placenta with levels approx 2-4 times those in the maternal serum. ... Spiramycin is excreted into breast milk. Nursing infants of mothers receiving 1.5 g/day for 3 days had spiramycin serum concns of 20 ug/ml. This concn was bacteriostatic.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
spiramycin在牛奶中的浓度通过微生物学方法测定。静脉给药后的平均滞留时间在牛奶中显著长于血浆中(P<0.01)。从浓度-时间曲线下面积计算的平均牛奶-血浆比值为36.5 +/- 15。对几种药代动力学参数进行了研究,以确定两种非血管内给药途径的生物等效性。肌内或皮下给药后吸收的剂量分数几乎为100%,并且对于非血管内给药途径是生物等效的,但是两种途径的吸收速率、最大浓度及其达到时间之间存在显著差异。牛奶中排出的spiramycin量在两种非血管内给药途径之间没有差异,但后者在牛奶中达到最大浓度的生物等效性不同。然而,两种给药途径在牛奶浓度超过各种引起乳腺感染的病原体的最小抑菌浓度(MIC)的时间长度上是生物等效的。
/MILK/ Spiramycin is a macrolide antibiotic that is active against most of the microorganisms isolated from the milk of mastitic cows. This work investigated the disposition of spiramycin in plasma & milk after iv, intramuscular & subcutaneous admin. Twelve healthy cows were given a single injection of spiramycin at a dose of 30,000 IU/kg by each route. Plasma & milk were collected post injection. Spiramycin concn in the plasma was determined by a high performance liquid chromatography method, & in the milk by a microbiological method. The mean residence time after iv admin was significantly longer (P<0.01) in the milk (20.7 +/- 2.7 h) than in plasma (4.0 +/- 1.6 h). An average milk-to-plasma ratio of 36.5 +/- 15 was calculated from the area concn-time curves. Several pharmacokinetic parameters were examined to determine the bioequivalence of the two extravascular routes. The dose fraction adsorbed after intramuscular or subcutaneous admin was almost 100% & was bioequivalent for the extravascular routes, but the rates of absorption, the max concns & the time to obtain them differed significantly between the two routes. Spiramycin quantities excreted in milk did not differ between the two extravascular routes but the latter were not bioequivalent for max concn in the milk. However, the two routes were bio-equivalent for the duration of time the milk concn exceeded the minimal inhibitory concn (MIC) of various pathogens causing infections in the mammary gland.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
血浆蛋白结合率从10%到25%。口服剂量600万单位在1.5到3小时后达到峰值血药浓度3.3微克/毫升;半衰期大约为5到8小时。组织中的高浓度可以在血浆浓度降至低水平后长时间维持。
Plasma protein binding ranges from 10 to 25%. An oral dose of 6 million units produces peak blood concentrations of 3.3 ug/mL after 1.5 to 3 hours; the half life is about 5 to 8 hours. High tissue concentrations are achieved and persist long after the plasma concentration has fallen to low levels.
来源:Hazardous Substances Data Bank (HSDB)

安全信息

  • 危险品标志:
    Xi
  • 安全说明:
    S24/25,S26,S36
  • 危险类别码:
    R36/37/38
  • WGK Germany:
    1
  • 海关编码:
    29419090

制备方法与用途

螺旋霉素是大环内酯类抗生素之一,由产二素产生。其抗菌谱与红霉素相似,但体外抗菌活性比红霉素弱,临床效果却更佳。对红霉素和青霉素耐药的菌株如金黄色葡萄球菌、链球菌等仍有良好的抗菌活性。螺旋霉素口服易吸收,毒性低,可用于治疗由多种细菌(包括金黄色葡萄球菌、肺炎链球菌、脑膜炎奈瑟氏球菌、淋病奈瑟氏球菌和大肠埃希氏菌)引起的感染。

大环内酯类抗生素

按化学结构,常见的大环内酯类药物包括12元环(如酒霉素)、14元环(如红霉素、罗红霉素、克拉霉素、地红霉素)、15元环(如阿奇霉素),以及16元环(如螺旋霉素、乙酰螺旋霉素、麦迪霉素、交沙霉素、吉他霉素)等多种亚类。这类药物主要作用于细菌核糖体50S亚基,通过抑制蛋白质合成发挥抗菌作用,临床常用于治疗肺炎链球菌等革兰阳性菌及流感嗜血杆菌引起的呼吸道和软组织感染,并对嗜肺军团菌、支原体、衣原体、非典型分枝杆菌、幽门螺杆菌(克拉霉素)和部分立克次体有效。螺旋霉素为16元环大环内酯类抗生素,广泛分布于体内,具有强大的抗菌作用和抗菌后效应,能够增强吞噬细胞的吞噬作用。

成分

螺旋霉素是一种复合种成分,并且不同成分具有的抗菌活性差别很大。螺旋霉素I的抗菌活性最强,螺旋霉素II及阻次之。不同国度,其组分构成及其需求有所差异。在国内,主要是需要螺旋霉素II及III两个组分,而螺旋霉素I的百分含量必须控制到低于12%的水平才能符合企业和国家的要求。因为螺旋霉素I的含量过高可能会对人体产生较强的副作用。

药理作用

螺旋霉素游离碱为白色至淡黄色粉末;味苦,微溶于水,易溶于多种有机溶剂。本品效价为每毫克含2700单位,临床常用其硫酸盐形式,稳定且易溶于水与乙醇。抗菌谱类似红霉素、泰乐菌素,对肺炎链球菌、化脓性链球菌、葡萄球菌、脑膜炎球菌、支原体等有抗菌作用。

应用

螺旋霉素在临床上的应用较为广泛,可用于治疗呼吸道感染引起的疾病。此外,在一些国家,螺旋霉素依旧是一种治疗牙源性感染的指定药物,如急性牙周炎、冠周炎、牙髓胳肿等。现螺旋霉素、阿莫西林及灭滴灵对牙周炎方面的治疗有一定的作用。

不良反应

螺旋霉素不良反应较红霉素轻,偶有胃肠道反应(如恶心、呕吐、食欲不振、便稀、腹泻),常发生于大剂量用药时。药物过敏反应少见,主要表现为药疹,一旦发现应立即停止用药。

药物联用

  1. 茶碱:可使茶碱作用增强,联用时应减少茶碱用量。
  2. 头孢唑啉:螺旋霉素具有快速抑菌作用,可能抑制头孢唑啉的快速杀菌效能。
  3. 泰乐菌素、卡那霉素、喹乙醇、杆菌肽锌、北里霉素、维吉尼霉素、黄霉素:均不宜与螺旋霉素配伍,存在配伍禁忌。

用途

主要用于治疗百日咳、肺炎、支气管炎、扁桃体炎、中耳炎、淋病、淋病性尿路炎等病症。本品可用于治疗由革兰阳性菌和某些革兰阴性菌引起的耳、鼻、喉和呼吸道感染,如急性支气管炎、急性支气管炎的急性发作、肺炎、猩红热、扁桃体炎、中耳炎、牙周炎和急性窦炎。本品也可用于治疗非淋菌性尿道炎。本品具有强大的体内抗菌作用和抗菌后效应(PAE),能够增强吞噬细胞的吞噬作用,广泛分布于体内,其在组织细胞内的浓度较红霉素高,副作用也较小。