(2R,3S,4R)-4-[(2R,5R,7S,8R,9S)-2-[(2R,5S)-5-ethyl-5-[(2S,3R,5S)-5-[(2S,3S,5R,6R)-6-hydroxy-6-(hydroxymethyl)-3,5-dimethyloxan-2-yl]-3-methyloxolan-2-yl]oxolan-2-yl]-7-hydroxy-2,8-dimethyl-1,10-dioxaspiro[4.5]decan-9-yl]-3-methoxy-2-methylpentanoic acid

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (2R,3S,4R)-4-[(2R,5R,7S,8R,9S)-2-[(2R,5S)-5-ethyl-5-[(2S,3R,5S)-5-[(2S,3S,5R,6R)-6-hydroxy-6-(hydroxymethyl)-3,5-dimethyloxan-2-yl]-3-methyloxolan-2-yl]oxolan-2-yl]-7-hydroxy-2,8-dimethyl-1,10-dioxaspiro[4.5]decan-9-yl]-3-methoxy-2-methylpentanoic acid
• 化学式: C₃₆H₆₂O₁₁
• 分子量: 670.9
• InChiKey: GAOZTHIDHYLHMS-GDMSFIFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  47
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  153
• 氢给体数：
  4
• 氢受体数：
  11

ADMET

代谢

单烯霉素是一种在兽医实践中广泛用作球虫抑制剂和生长促进剂的离子载体抗生素。本研究探讨了单烯霉素在马、猪、肉鸡、牛和大鼠的肝微粒体中的氧化代谢。通过测定释放的甲醛的量来评估，单烯霉素的O-脱甲基化速率在所有物种中几乎处于相同的数量级，但总单烯霉素代谢（通过高效液相色谱法测量底物消失速率来估计）在牛中最高，在大鼠、肉鸡和猪中居中，在马中最低。当以转化数（每分钟每纳米摩尔细胞色素P450-1代谢的单烯霉素纳米摩尔数）表示时，催化效率（肉鸡>>牛>>猪≈大鼠>马）被发现与已知的不同物种对离子载体毒副作用易感性的差异呈反比关系，这种差异的特点是马的口服LD50为2-3 mg/kg体重，牛为50-80 mg/kg体重，肉鸡为200 mg/kg体重。肉鸡和牛的微粒体也显示出对两种P450 3A依赖性底物（红霉素和三乙酰奥兰多霉素）最高的催化效率，以及与抗大鼠P450 3A1/2抗体交叉反应的最高免疫检测蛋白水平。

The oxidative metabolism of monensin, an ionophore antibiotic extensively used in veterinary practice as a coccidiostat and a growth promoter, was studied in hepatic microsomal preparations from horses, pigs, broiler chicks, cattle and rats. As assayed by the measurement of the amount of the released formaldehyde, the rate of monensin O-demethylation was nearly of the same order of magnitude in all species, but total monensin metabolism, which was estimated by measuring the rate of substrate disappearance by a high-performance liquid chromatography (HPLC) method, was highest in cattle, intermediate in rats, chicks and pigs, and lowest in horses. When expressed as turnover number (nmol of metabolized monensin/min nmol cytochrome P450-1), the catalytic efficiency (chick >> cattle >> pig approximately rat > horse) was found to correlate inversely with the well known interspecies differences in the susceptibility to the toxic effects of the ionophore, which is characterized by an oral LD50 of 2-3 mg/kg bodyweight (bw) in horses, 50-80 mg/kg bw in cattle and 200 mg/kg bw in chicks. Chick and cattle microsomes also displayed both the highest catalytic efficiency toward two P450 3A dependent substrates (erythromycin and triacetyloleandomycin) and the highest immunodetectable levels of proteins cross-reacting with anti rat P450 3A1/2. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

莫能菌素在苯巴比妥处理的大鼠肝微粒体中的O-脱甲基作用比未处理的大鼠要强，并且这一过程依赖于还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH），这表明莫能菌素是细胞色素P450（CYP）酶的底物。莫能菌素的氧化代谢至少部分是通过CYP3A进行的，因为用CYP3A的化学诱导剂处理大鼠肝微粒体会显著增加莫能菌素的O-脱甲基作用。有人推测，莫能菌素与其他CYP3A底物之间的竞争可能解释了在几种家养动物中同时给予莫能菌素和其他化疗药物后发生的意外中毒事件，因为在大鼠中，当存在其他CYP3A底物时，莫能菌素的代谢会显著减少。

The O-demethylation of monensin is greater in microsomes from phenobarbital-treated rats than in untreated rats and is dependent on reduced nicotinamide adenine dinucleotide phosphate (NADPH), suggesting that monensin is a cytochrome P450 (CYP) enzyme substrate. The oxidative metabolism of monensin appears to occur at least in part by CYP3A, since treatment of rat hepatic microsomes with chemical inducers of CYP3A significantly increased monensin O-demethylation. It has been speculated that competition between monensin and other CYP3A substrates may explain accidental poisonings that have occurred in several domestic species following coadministration of monensin and other chemotherapeutic agents, since monensin metabolism is significantly decreased in the presence of other CYP3A substrates in rats.

来源:Hazardous Substances Data Bank (HSDB)

代谢

莫能菌素代谢物主要来自于离子载体骨架上甲氧基团的O-脱甲基化以及/或在多个位置的羟基化。尽管很难获得足够的莫能菌素代谢物来测试活性，但通过大鼠肝脏微粒体产生的四种代谢物（包括莫能菌素生产过程中的一个副产品O-去甲基莫能菌素）已经过测试，它们的抗菌、抗球虫、细胞毒性、强心剂和离子载体活性至少比母化合物低10到20倍，这表明代谢作用消除了莫能菌素的大部分生物活性。

Monensin metabolites result mainly from O-demethylation at the methoxylic group and/or hydroxylation at several places on the ionophore backbone. ... Although it is difficult to obtain sufficient monensin metabolites to test activity, four metabolites generated by rat liver microsomes, including a by-product of monensin production (O-desmethylmonensin), have been tested and have at least 10- to 20-fold less antibacterial, anticoccidial, cytotoxic, cardiotonic and ionophoric activity than the parent compound, indicating that metabolism eliminates most of the biological activity of monensin.

来源:Hazardous Substances Data Bank (HSDB)

代谢

莫能菌素在肝脏中广泛代谢，产生了超过50种不同的代谢物，这些代谢物已在鸡、牛、大鼠、猪、狗、火鸡、羊和马的肝脏、胆汁和粪便中被检测到。在大多数物种（鸡、大鼠、狗、火鸡和猪）中，少于10%的莫能菌素以原形化合物排出，而在犊牛的一项研究中表明，粪便中识别出的(14)C有50-68%是未代谢的莫能菌素。这种在不同物种中代谢的莫能菌素量的差异可能是由于分子在不同物种中的吸收差异造成的。通过高效液相色谱(HPLC)分析方法测量底物消失速率来估算的总微粒体莫能菌素代谢率在牛中最高，在大鼠、鸡和猪中居中，在马中最低。尽管存在定量差异，实验室和非实验室动物物种之间的代谢物模式在质量上是相似的。没有单一的代谢物占据主导地位。

Monensin is extensively metabolized in the liver, producing more than 50 different metabolites that have been detected in the liver, bile and faeces of chickens, cattle, rats, pigs, dogs, turkeys, sheep and horses. In most species (chickens, rats, dogs, turkeys and pigs), less than 10% of monensin is excreted as the parent compound, whereas a study in calves indicated that 50-68% of the (14)C identified in the feces was unmetabolized monensin. This difference in amount of metabolized monensin may have been a result of differences in absorption of the molecule in different species. Total microsomal monensin metabolism, estimated by measuring the rate of substrate disappearance by a high-performance liquid chromatographic (HPLC) analytical method, is highest in cattle, intermediate in rats, chickens and pigs, and lowest in horses. The pattern of metabolites is qualitatively similar between laboratory and non-laboratory animal species, although quantitative differences exist. No single metabolite dominates the metabolic profile.

来源:Hazardous Substances Data Bank (HSDB)

代谢

单钠莫能菌素在人类肝脏微粒体的代谢已与马和狗的微粒体中的代谢进行了比较。来自多个捐赠者（男女、白人、西班牙裔和非裔美国人，年龄15-66岁）的混合人微粒体样本、混合狗微粒体样本以及来自单一捐赠者的马微粒体与0.5、1和10微克/毫升单钠莫能菌素在存在或不存在NADPH的情况下进行孵化。在0、5、10、20、40和60分钟时，通过液相色谱/质谱（LC-MS）分析检查了代谢物谱。单钠莫能菌素在所有物种中按一级动力学代谢，并且代谢是广泛的（60分钟时为93-99%）。人类中单钠莫能菌素的转化率与狗相似，而在马中的转化率仅为狗和人类的10%。

The metabolism of monensin sodium in human liver microsomes has been compared with metabolism in the microsomes of horses and dogs. A pooled human microsomal sample from multiple donors (male and female, Caucasian, Hispanic and African American, 15-66 years old), pooled dog microsome sample and equine microsomes from a single donor were incubated with 0.5, 1 and 10 ug monensin/mL in the presence or absence of NADPH. The metabolite profiles were examined at 0, 5, 10, 20, 40 and 60 min by liquid chromatography/mass spectrometry (LC-MS) analysis. Monensin was metabolized by first-order kinetics in all species, and metabolism was extensive (93-99% by 60 min). The turnover of monensin in humans was similar to that in dogs, whereas the turnover in horses was only 10% of that in dogs and humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：莫能菌素是一种多醚羧酸离子载体抗生素。莫能菌素是由四种类似物A、B、C和D组成的混合物，其中莫能菌素A是主要成分（98%）。根据纯化的方法，莫能菌素可以以菌丝体、结晶体和再结晶体的形式存在。它用于治疗家禽（鸡、火鸡和鹌鹑）和反刍动物（牛、羊和山羊）的球虫病。莫能菌素还用于控制牛的酮病和胃胀，并作为牛和羊的生长促进剂饲料添加剂。莫能菌素主要对革兰氏阳性细菌有效。 人类暴露和毒性：一名17岁的男孩在摄入莫能菌素钠后11天出现肌红蛋白尿、肾衰竭和死亡。在另一例中，一名患者服用了比牛致死剂量高三倍的莫能菌素，出现了与兽医医学中报道的临床图片相似的症状。出现了早期和极度严重的横纹肌溶解，随后是急性肾衰竭、心衰和死亡。尸检时观察到的主要变化是广泛的骨骼肌坏死，心肌水平的补体沉积，肺水肿和急性管状损伤。 动物研究：在成熟的猕猴中研究了急性毒性。将成对的猴子通过灌胃暴露于20、40或60 mg/kg bw的单剂量莫能菌素，并监测7天。所有动物在给药后24小时内都存活并出现腹泻。成年山羊通过胃灌胃每天连续五天给予钠莫能菌素，13.5 mg/kg。莫能菌素暴露引起了腹泻、心动过速和瘤胃运动以及体温的降低。在一项吸入暴露研究中，大鼠暴露于正常空气或含有平均浓度为79 mg/cu m的颗粒状菌丝体莫能菌素钠的空气，持续2周（每天1小时，每周5天）。在研究的第二周，10只处理过的雌性中有9只出现厌食和体重下降。在两只雄性和两只雌性中看到了骨骼肌的轻微局灶性肌炎，但对照组中没有。在雄性大鼠中观察到多灶性心肌变化。在一项亚慢性研究中，雌雄小鼠被喂食含有0、37.5、75、150或300 mg/kg菌丝体莫能菌素钠的饮食，持续3个月。所有剂量组都出现了剂量依赖性的体重增长下降。在研究结束时，下降幅度从最低剂量组雌性和雄性分别的27%和21%到最高剂量组两性的99%。在一项慢性毒性研究中，雌雄大鼠在含有25、56或125 mg/kg结晶体莫能菌素钠的饮食中饲养，而对照组大鼠接受正常饮食，持续2年。在125 mg/kg饮食中的动物的体重和体重增长显著降低，而在中间剂量组的大鼠在前4个月内暂时降低。在处理和未处理的动物中观察到了良性肿瘤和恶性肿瘤，但莫能菌素管理与肿瘤类型或严重程度之间没有关联。莫能菌素对马有毒。临床表现为心动过速和心律不齐，呻吟，不协调，出汗，躺卧，和四肢划水样动作死亡。尸检发现主要在骨骼肌和心肌。研究了发育期间暴露于莫能菌素的影响。在达到185 g的配种体重之前以及怀孕和哺乳期间，将雌性大鼠以0、100或300 mg/kg的浓度给予莫能菌素。在高剂量组中，雌性体重在治疗8天后显著下降。在高剂量组中，雄性和雌性幼崽的体重从出生后第10天降至出生后第21天。低剂量组的雄性后代仅在出生后第21天表现出体重下降。在幼崽中没有检测到外部的畸形迹象。还进行了一项研究，以探索莫能菌素，一种强大的高尔基体干扰剂对雄性生育的影响。雄性大鼠以2.5、5和10 mg/kg b wt的剂量给予莫能菌素。在治疗67天后处死动物。电子显微镜的发现，如膜破裂、肿胀和高尔基体的解体，强烈提示莫能菌素干扰了精原细胞中高尔基体的功能。来自精子数量和活力以及生育研究和产生的窝大小的数据进一步指出莫能菌素对雄性大鼠的抗生育作用。遗传毒性试验为阴性。

IDENTIFICATION AND USE: Monensin is a polyether carboxylic ionophore antibiotic. Monensin is a mixture of four analogues, A, B, C and D, with monensin A being the major component (98%). Depending on the method of purification, monensin can exist in mycelial, crystalline and recrystallized forms. It is used for the treatment of coccidiosis in poultry (chickens, turkeys and quail) and ruminants (cattle, sheep and goats). Monensin is also used to control ketosis and bloat in cattle and as a growth promoter feed additive in cattle and sheep. Monensin is mainly effective against Gram-positive bacteria. HUMAN EXPOSURE AND TOXICITY: 17 year-old boy who developed myoglobinuria, renal failure and death 11 days after ingesting sodium monensin. In another case, a patient took a dose of monensin three times higher than a dose considered lethal for cattle and developed a clinical picture similar to that reported in veterinary medicine. There was an early and extremely severe rhabdomyolysis followed by acute renal failure, heart failure, and death. The main changes observed at autopsy were extensive skeletal muscle necrosis, complement deposition at the myocardial level, pulmonary edema, & acute tubular damage. ANIMAL STUDIES: Acute toxicity was examined in mature rhesus monkeys. Pairs of monkeys were exposed to a single dose of 20, 40 or 60 mg monensin/kg bw by gavage and were monitored for 7 days. All animals survived and developed diarrhea within 24 hr after dosing. Adult goats were administered sodium monensin, 13.5 mg kg (-1), daily for five consecutive days via gastric gavage. Monensin exposure caused diarrhea, tachycardia and reduction in ruminal movements and body temperature. In an inhalational exposure study, rats were exposed to either normal air or air containing particulate mycelial monensin sodium at a mean concentration of 79 mg/cu m for 2 weeks (1 hr/day, 5 days/week). Nine of 10 treated females became anorexic and lost weight during the 2nd week of the study. Slight focal myositis of the skeletal muscle was seen in two males and two females but none of the controls. Multifocal myocardial changes were observed in male rats treated with monensin. In a subchronic study, male and female mice were fed diets containing 0, 37.5, 75, 150 or 300 mg mycelial monensin sodium/kg for 3 months. A dose-dependent decrease in body weight gain occurred in all dose groups. At the end of the study, the decrease ranged from 27% and 21% in the lowest dose group in females and males, respectively, to 99% in the highest dose group in both sexes. In a chronic toxicity study, male and female rats were maintained on a diet containing 25, 56 or 125 mg crystalline monensin sodium/kg, whereas control rats received a normal diet for 2 years. Body weight and weight gain were significantly decreased in animals receiving 125 mg monensin/kg in their diet and were transiently decreased during the first 4 months in rats in the middle dose group. Benign and malignant neoplasms were observed in treated and untreated animals, with no association between monensin administration and neoplasm type or severity. Monensin is toxic in horses. Clinical signs were tachycardia and cardiac arrythmia, groaning, incoordination, sudoresis, recumbency, and paddling movements with the limbs before death. Main necropsy findings were in the skeletal muscles and myocardium. The effects of exposure to monensin during development were studied in rats. Groups of female rats received monensin at concentrations of 0, 100 or 300 mg/kg until premating weights achieved 185 g and during pregnancy and lactation. Female body weight was significantly decreased in the highest dose group after 8 days of treatment. The body weights of male and female pups in the highest dose group were reduced from postnatal day 10 until postnatal day 21. Male offspring in the low dose group showed body weight reduction only on postnatal day 21. No external signs of malformation were detected in the pups. A study was also undertaken to explore the effects of monensin, a potent Golgi disturbing agent on male fertility. Male rats were administered monensin at the dose levels of 2.5, 5, and 10 mg/kg b wt. Animals were sacrificed after 67 days of the treatment. The findings from electron microscopy such as membrane disruption, swelling and disintegration of Golgi apparatus strongly suggest the interference of monensin with the functioning of Golgi apparatus in the spermatogenic cells. Data from the sperm number and motility as well as the fertility studies and the resulted litter size further points towards the antifertility effects of monensin in male rats. Genotoxicity tests were negative.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 副作用

神经毒素 - 其他中枢神经系统神经毒素

Neurotoxin - Other CNS neurotoxin

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 相互作用

进行了一项实验，以评估莫能菌素（150 mg/kg）与生长促进剂（GPs）锌杆菌肽（BAC，50 mg/kg）、维吉尼霉素（VIR，25 mg/kg）和阿伏帕霉素（AVO，20 mg/kg）从7至28日龄期间喂养对肉鸡性能、营养物质利用、去皮去内脏胴体（DEC）产量和各种器官大小的影响。还确定了在未添加莫能菌素的饲料中GPs对49日龄内性能和胴体的影响。莫能菌素显著（P < 0.05）降低了7至28日龄期间的食物摄入量、体重增加和食物效率。没有任何一种GPs能够抵消这些影响。然而，AVO略微改善了这些影响。AVO还显著增加了7至28日龄期间的食物摄入量，并提高了增重和食物效率，但在28至49日龄或7至49日龄期间则没有影响。VIR和BAC在任一日龄期间对性能都没有影响。莫能菌素不影响日粮干物质、脂肪或能量的利用，但显著降低了氮的利用。AVO改善了氮和脂肪的利用，并增加了日粮的AME(n)含量。VIR也增加了AME(n)含量。这些营养物质的利用不受莫能菌素与GPs之间相互作用的影响。莫能菌素在31日龄时对DEC的产量或相对肝脏大小没有影响。它显著增加了小肠（SI）的相对长度并降低了其特定重量。AVO在31日龄时显著增加了产量，但在53日龄时没有影响。BAC和VIR对此变量没有影响。AVO和VIR（但不是BAC）在两个日龄期间都减少了SI的大小、长度和特定重量，有时这种减少是显著的。我们的结论是：BAC、VIR和AVO不能抵消莫能菌素的毒性作用。GPs在提高性能方面的效果会随着年龄的增长而减少甚至消失，而它们在减少SI大小方面的效果在49日龄的鸡中仍然明显。

An experiment was carried out with male broiler chicks to evaluate the combined effect of monensin (150 mg/kg) & the growth promoters (GPs) Zn bacitracin (BAC, 50 mg/kg), virginiamycin (VIR, 25 mg/kg) & avoparcin (AVO, 20 mg/kg) fed from 7 to 28 days of age on performance, utilization of dietary nutrients, yield of defeathered eviscerated carcases (DEC) & size of various organs. The effect of the GPs in the monensin-unsupplemented diets fed up to 49 d of age on performance & carcase was also determined. Monensin significantly (P < 0.05) depressed food intake, weight gain & food efficiency from 7 to 28 d of age. None of the GPs was able to counteract these effects. However, AVO slightly ameliorated them. AVO also significantly increased food intake & improved gain & food efficiency during 7 to 28, but not 28 to 49 or 7 to 49 d of age. VIR & BAC did not affect performance in either age period. Monensin did not affect the utilisation of dietary dry matter, fat or energy, but it significantly decreased nitrogen utilisation. AVO improved nitrogen & fat utilisation & increased dietary AME(n) content. AME(n) was also increased by VIR. The utilisation of these nutrients was not affected by the interactions between monensin & the GPs. Monensin did not affect yield of the DEC or the relative liver size at 31 d of age. It significantly increased the relative length of the small intestine (SI) & decreased its specific weight. AVO significantly increased yield at 31, but not at 53 d of age. BAC & VIR did not affect this variable. AVO & VIR, but not BAC, at both age periods reduced, at times significantly, the size, length & specific weight of the SI. Our conclusions: BAC, VIR & AVO do not counteract the toxic effect of monensin. The effect of GPs in improving performance decreases & even disappears with age, while their effect in reducing the size of the SI is still evident in 49 day old birds.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在这项研究中，共同给予离子载体类药物蒙纳米斯并没有改变恩诺沙星或诺氟沙星的血药水平。

In this study, co-admin of the ionophore monensin was not shown to alter blood levels of enrofloxacin or norfloxacin.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

研究了莫能菌素和泰妙菌素在大鼠体内的毒性相互作用特性。在第一阶段，进行了一项为期三天的比较口服重复剂量毒性研究，分别研究了莫能菌素和泰妙菌素的效果（莫能菌素按10、30和50毫克/千克体重，泰妙菌素按40、120和200毫克/千克体重）。在第二阶段，同时给药这两种化合物以研究毒性相互作用（莫能菌素10毫克/千克和泰妙菌素40毫克/千克体重）。结果表明，莫能菌素在大鼠体内的剂量为30和50毫克/千克时具有毒性。泰妙菌素在剂量达到200毫克/千克时仍能良好耐受。联合给药后，出现了毒性迹象（包括雌性动物的致死性）。莫能菌素在50毫克/千克的剂量下引起剂量依赖性的心肌毒性和骨骼肌的空泡变性。两种化合物在高剂量下都对肝脏产生了毒性影响。同时给药后，对肝脏的影响轻微（仅限雌性），心肌出现水样变性和骨骼肌的空泡变性。在骨骼肌中观察到的变化比单独给予50毫克/千克莫能菌素时更为明显。

The characteristics of the toxic interaction between monensin & tiamulin were investigated in rats. A three-day comparative oral repeated-dose toxicity study was performed in Phase I, when the effects of monensin & tiamulin were studied separately (monensin 10, 30, & 50 mg/kg or tiamulin 40, 120, & 200 mg/kg body weight, respectively). In Phase II, the two compounds were administered simultaneously to study the toxic interaction (monensin 10 mg/kg & tiamulin 40 mg/kg bw, respectively). Monensin proved to be toxic to rats at doses of 30 & 50 mg/kg. Tiamulin was well tolerated up to the dose of 200 mg/kg. After combined administration, signs of toxicity were seen (including lethality in females). Monensin caused a dose-dependent cardiotoxic effect & vacuolar degeneration of the skeletal muscles in the animals given 50 mg/kg. Both compounds exerted a toxic effect on the liver in high doses. After simultaneous administration of the two compounds, there was a mild effect on the liver (females only), hydropic degeneration of the myocardium & vacuolar degeneration of the skeletal muscles. The alteration seen in the skeletal muscles was more marked than that seen after the administration of 50 mg/kg monensin alone.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

单剂量40 mg/kg体重的莫能菌素以肌内和静脉途径给药后，莫能菌素的药代动力学参数包括半衰期、表观分布容积、总清除率、系统生物利用度和组织残留物在肉鸡中得到了确定。静脉注射后，莫能菌素的动力学分布遵循一个两室开放模型，吸收半衰期为0.59小时，分布容积为4.11 l/kg，总清除率为28.36 ml/kg/min。莫能菌素在肌内给药后0.5小时达到最高血清浓度，吸收半衰期为0.27小时，消除半衰期为2.11小时。肌内给药后的系统生物利用度为65.1%。在体外测定的莫能菌素与血清蛋白的结合倾向为22.8%。在单次肌内给予纯莫能菌素（40 mg/kg体重）后，鸡的血清和组织中的莫能菌素浓度高于连续两周饲喂添加莫能菌素的预混剂（120 mg/kg）后的浓度。在口服给药后2、4、6和8小时收集的测试身体组织中检测到莫能菌素残留物。在肝脏中发现的浓度最高。此外，在最后一次口服给药后24小时，仅在肝脏、肾脏和脂肪中检测到莫能菌素残留物。在48小时后，除了在72小时完全清除的肝脏外，在组织中无法检测到莫能菌素残留物。

The pharmacokinetics of monensin, including half-life, apparent volume of distribution, total body clearance, systemic bioavailability and tissue residues were determined in broiler chickens. The drug was given by intracrop and intravenous routes in a single dose of 40 mg/kg body weight. Following intravenous injection the kinetic disposition of monensin followed a two compartments open model with absorption half life of 0.59 hr, volume of distribution of 4.11 l/kg and total body clearance of 28.36 ml/kg/min. The highest serum concentrations of monensin were reached 0.5 hr after intracrop dosage with an absorption half-life of 0.27 hr and an elimination half life of 2.11 hr. The systemic bioavailability was 65.1% after intracrop administration. Serum protein-binding tendency of monensin calculated in vitro was 22.8%. Monensin concentrations in the serum and tissues of chickens after a single intracrop dose of pure monensin (40 mg/kg body weight) were higher than those after feeding a supplemented monensin premix (120 mg/kg) for 2 weeks. Monensin residues were detected in tested body tissues, collected 2, 4, 6 and 8 hr after oral administration. The highest concentration was found in the liver. In addition, monensin residues were detected only in liver, kidney and fat 24 hr after the last oral dose. No monensin residues could be detected in tissues after 48 hr, except in liver which cleared completely by 72 hr.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

六只鸡在饲料中暴露于每千克121毫克的3H-莫能菌素钠，持续2天。仅回收了52-73%的放射性；其中，97%在粪便中找到。放射性平衡差的原因未知。/莫能菌素钠/

Six chickens were exposed to (3)H-monensin sodium at 121 mg/kg in the diet for 2 days. Only 52-73% of the radioactivity was recovered; of this, 97% was found in the faeces. The reason for poor radioactivity balance was unknown. /Monensin sodium/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

肉鸡在饲料中按120毫克/千克浓度喂服14C-莫能菌素钠，持续4天（两公三母）或6天（三公三母）。停止喂食处理后6小时，在肝脏、肾脏、脂肪和皮肤中检测到放射性，其中肝脏中检测到的放射性最高（0.5毫克/千克肝脏）。在肌肉组织中未检测到放射性。/莫能菌素钠/

Broiler chickens were administered (14)C-monensin sodium at a concentration of 120 mg/kg in the diet for 4 days (two males, three females) or 6 days (three males, three females). Six hours after withdrawal from the treated feed, radioactivity was detected in the liver, kidney, fat and skin, with the highest level detected in the liver (0.5 mg/kg liver). No radioactivity was detected in the muscle tissue. /Monensin sodium/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

十只白色莱航公鸡和两只白色莱航母鸡通过口服方式接触了一次剂量的放射性碳-14标记的莫能菌素，该药物被封装在明胶胶囊中（剂量范围：2.6-100毫克）。部分鸟类进行了结肠造口，而其他鸟类插入了胆管导管。鸡对摄入的放射性碳-14标记的莫能菌素的吸收率在11%到31%之间。主要的排泄途径是在粪便中，一小部分通过尿液和呼吸排出。

Ten White Leghorn roosters and two White Leghorn hens were exposed orally to a single dose of (14)C-monensin in a gelatine capsule (dose range: 2.6-100 mg). Some birds were colostomized, whereas others had bile cannulae inserted. Absorption in the chickens ranged from 11% to 31% of the ingested (14)C-monensin. The primary route of excretion was in the faeces, with a small proportion excreted in the urine and by respiration.

来源:Hazardous Substances Data Bank (HSDB)

文献信息

• COMPOSITION AND METHOD FOR CO-ADMINISTRATION WITH A GROWTH PROMOTANT
  申请人：Puntenney Steven B.

  公开号：US20150209416A1

  公开（公告）日：2015-07-30

  Embodiments of a composition comprising silica, mineral clay, mannans, or any combination thereof are disclosed. The composition may further comprise glucan. The composition is administered to an animal that will be administered, or has been administered, a growth promotant. The growth promotant may be a β-agonist, antibiotic, steroid or hormone. The composition is fed to the animal for a period of time before administration of the growth promotant, during administration of the growth promotant, and/or after administration of the growth promotant. Administration of the composition to the animal ameliorates, or prevents development of, at least one deleterious symptom or sign, such as a deleterious symptom or sign potentially associated with administration of the growth promotant. Embodiments of a composition comprising (i) a growth promotant and (ii) glucan, silica, mineral clay, mannans, or any combination thereof also are disclosed.