Solutions and aqueous suspensions begin to lose activity soon after preparation. Aqueous suspensions are stable for 10 minutes on heating to 100 °C at pH 7; also stable in moderately alkaline media, but labile at pH 9 and pH 2. Heat, light, and oxygen accelerate decomposition.
旋光度：
Optical rotation at 25 °C/D: -10 deg (glacial acetic acid); +21 deg (pyridine); +12 deg (dimethylformamide); max absorption (ethanol): 290, 307 and 322 nm; optical rotation at 25 °C/D: -7 deg (0.1 N HCl in methanol)
Nystatin therapy has been associated with a low rate of serum enzyme abnormalities, although it has been difficult to attribute these elevations to nystatin. Despite its use for several decades, there have been no convincing cases of acute hepatic injury linked to nystatin therapy. While nystatin is usually is not normally absorbed, low concentrations may enter the circulation in patients with inflammation and damage to the gastrointestinal tract. Nevertheless, nystatin is considered very safe and is unlikely to cause hepatic injury.
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
人类毒性摘录
/病例报告/ ...已报告了几例局部过敏反应的病例。
/CASE REPORTS/ ...Few cases of local allergic reactions have been reported.
/EPIDEMIOLOGY STUDIES/ Prescription frequencies in the first trimester were compared for miconazole, clotrimazole, nystatin, candicidin, aminacrine compounds, and metronidazole before deliveries involving congenital anomalies versus those not linked to congenital anomalies. Prescriptions before spontaneous abortions were compared with those in the first trimester of deliveries and with those before legal abortions. No statistically significant association was observed with any of these agents for the overall frequency of birth defects or for specific birth defects analyzed (cardiovascular defects, oral clefts, and spina bifida). Two hundred fifty miconazole exposures among 4264 spontaneous abortions, compared with 2236 in the first trimester of 55,736 deliveries, provided an estimated relative risk of 1.4 (95% confidence limits 1.2-1.5). One hundred twelve treatments with clotrimazole among the spontaneous abortions, compared with 1086 among the deliveries, provided a relative risk of 1.4 (95% confidence limits 1.1-1.6). In contrast, large numbers of exposures to nystatin and aminacrine compounds did not show this association, suggesting that spontaneous abortions are caused by the imidazole agents miconazole and clotrimazole rather than the condition being treated. Because many associations were examined without previous hypotheses, and because the data were inadequate to show an elevated risk for clotrimazole when comparing spontaneous with legal abortion exposures, these findings are considered to be a signal for further studies rather than definitive in themselves.
Nystatin is poorly absorbed from the GI tract, and detectable blood concentrations are not obtained after usual doses. Following oral administration, nystatin is excreted almost entirely in feces as unchanged drug.
In healthy individuals, mean salivary nystatin concentrations in excess of those required in vitro for growth inhibition of clinically important Candida persist for approximately 2 hours after the beginning of oral dissolution of two nystatin lozenges (400,000 units) administered simultaneously.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
未通过完整皮肤或粘膜的局部应用被吸收。
Not absorbed following topical application to intact skin or mucous membranes.
Semisynthetic Amides of Amphotericin B and Nystatin A1: A Comparative Study of In Vitro Activity/Toxicity Ratio in Relation to Selectivity to Ergosterol Membranes
ergosterol than cholesterol. Notably, the high nephro- and hemolytic toxicity of polyenes and their low solubility in water have led to efforts to improve their properties. We present the synthesis of newamphotericin and nystatin amides and a comparativestudy of the effects of identical modifications of AmB and Nys on the relationship between their structure and properties. Generally, increases in
多烯抗真菌剂两性霉素 B (AmB) 已使用 60 多年，并且由于其广泛的抗真菌活性和较低的耐药率，仍然是系统性真菌病的有价值的临床治疗方法。关于它究竟如何杀死真菌细胞尚无共识，但可以肯定的是，AmB 和密切相关的制霉菌素 (Nys) 可以在膜中形成孔隙，并且对麦角甾醇的亲和力高于对胆固醇的亲和力。值得注意的是，多烯的高肾毒性和溶血毒性及其在水中的低溶解度导致人们努力改善其性能。我们介绍了新的两性霉素和制霉菌素酰胺的合成，并比较研究了 AmB 和 Nys 的相同修饰对其结构和性质之间关系的影响。一般来说，活性/毒性比率的增加与麦角甾醇与含胆固醇膜的选择性透化比率的增加非常一致。我们还表明，引入的修饰对突变酵母菌株的敏感性有影响，麦角甾醇生物合成对所研究的多烯发生了改变，表明对中间麦角甾醇前体的不同亲和力。三种新型水溶性制霉菌素衍生物在安全性方面表现出显着改善，被选为有前途的药物开发候选物。
