암포테리신β

Deep yellow prisms or needles from n,n-dimethylformamide

YELLOW TO ORANGE POWDER

less than 1 mg/mL at 70 °F (NTP, 1992)

In N,N-dimethylformamide 2-4 mg/ml, in N,N-dimethylformamide + hydrochloric acid 60-80 mg/ml, in dimethyl sulfoxide 30-40 mg/ml

INSOL IN ANHYDROUS ALC, ETHER, BENZENE & TOLUENE; SLIGHTLY SOL IN METHANOL

Insol in water at pH 6-7; solubility in water at pH 2 or pH 11 about 0.1 mg/ml; water sol increased by sodium desoxycholate

In water, 750 mg/L at 25 °C

Breast Feeding; Lactation; Antifungal Agents

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Antifungal medicines

greater than 338 °F (decomposes) (NTP, 1992)

170 °C (gradual decomposition)

170.0 °C

Amphotericin b is a bright yellow powder. (NTP, 1992)

Solid

Solids and solutions appear stable for long periods between pH 4 and 10 when stored at moderate temperature out of light and air.

Drug is unstable under unfavorable conditions (eg, exposure to heat, light, low ph). Dry powder should be refrigerated and stored no more than 24 hr.

Warning

H315 (97.4%): Causes skin irritation [Warning Skin corrosion/irritation]

P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 152 reports by companies from 23 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Chemical: Amphotericin B

Amphotericin B: Does not have an individual approval but may be used under an appropriate group standard

SYMPTOMS: Symptoms of exposure to this compound (through ingestion) may include fever; anorexia; flushing; generalized pain; convulsions; chills; phlebitis; headache; anemia; anaphylaxis; thrombocytopenia; vomiting; mild renal tubular acidosis; decreased renal function; hypokalemia; hypomagnesemia; nerve palsies, including foot drop; weight loss; malaise; dyspepsia; diarrhea; azotemia; hyposthenuria; nephrocalcinosis; and less frequently, anuria; oliguria; arrhythmias; ventricular fibrillation; cardiac arrest; hypertension; hypotension; coagulation effects; leukopenia; agranulocytosis; eosinophilia; melena or hemorrhagic gastroenteritis; rash; hearing loss; tinnitus; transient vertigo; and blurred vision.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl amphotericin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Benson JM, Nahata MC; Clinical Use of Systemic Antifungal Agents. Clin Pharm 7 (Jun): 424-38 (1988). The chemistry, pharmacology, mechanism of action, pharmacokinetics, clinical uses, adverse effects, and drug interactions of amphotericin B are reviewed.

Branch RA; Prevention of Amphotericin B Induced Renal Impairment: Review on the Use of Sodium Supplementation. Arch Intern Med 148 (Nov): 2389-94 (1988). The incidence and mechanism of kidney failure attributed to amphotericin B (Fungizone), guidelines for reducing the risk of renal impairment when the drug is used, and the potential use of sodium, either as sodium chloride or ticarcillin disodium, to reduce the risk of nephrotoxicity are discussed.

Gallis HA et al; Amphotericin B: 30 Years of Clinical Experience. Rev Infect Dis12 (2): 308-29 (1990). This paper discusses the clinical uses of amphotericin B, including its application in AIDS related fungal infections, in neutropenic cancer patients who are persistently febrile, and in infections of the central nervous system, lung, peritoneum, genitourinary system, eye, and skin. The paper also reviews the drug's adverse reactions, with a discussion of administration techniques that may reduce these reactions, and its spectrum of activity, pharmacokinetics, and dosage and administration.

Georgiev VS; Treatment and Developmental Therapeutics in Aspergillosis. 1. Amphotericin B and its Derivatives. Respiration 59 (5): 291-302 (1992). The clinical efficacy of amphotericin B, its toxicities and various routes of applications, are discussed. Different combinations of amphotericin B with other drugs have also been reviewed, along with the anti-Aspergillus activity of various other antibiotics and some ester derivatives of amphotericin B.

For more Special Reports (Complete) data for AMPHOTERICIN B (12 total), please visit the HSDB record page.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

Conventional amphotericin B powder for injection should be stored at 2-8 °C. Reconstituted colloidal dispersions of conventional amphotericin B should be protected from light and are stable for 24 hours at room temperature or 1 week when refrigerated at 2-8 °C. Although the manufacturers state that reconstituted dispersions or IV infusions of amphotericin B should be protected from light during administration, potency is unaffected if the infusion is exposed to light for less than 8-24 hours.

Commercially available lyophilized amphotericin B cholesteryl sulfate complex should be stored at 15-30 °C. Following reconstitution with sterile water for injection, the colloidal dispersion should be refrigerated at 2-8 °C and used within 24 hours; reconstituted amphotericin B cholesteryl sulfate complex should not be frozen. Reconstituted amphotericin B cholesteryl sulfate complex that has been further diluted in 5% dextrose injection should be stored at 2-8 °C and used within 24 hours; any partially used vials of the drug should be discarded.

Do not reconstitute with saline or add saline to the reconstituted concentration, or mix with other drugs. The use of any solution other than those recommended, or the presence of a bacteriostatic agent in the solution, may cause precipitation of am B isome.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, FIRST REMOVE ALL SOURCES OF IGNITION. You should then dampen the solid spill material with 60-70% methanol, then transfer the dampened material to a suitable container. Use absorbent paper dampened with methanol to pick up any remaining material. Your contaminated clothing and absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent-wash contaminated surfaces with 60-70% methanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

Since nephrotoxic effects may be additive, the concurrent or sequential use of amphotericin B and other drugs with similar toxic potentials (eg, aminoglycosides, capreomycin, colistill, cisplatin, cyclosporine, methoxyflurane, pentamidine, polymyxin B, vancomycin) should be avoided, if possible.

Corticosteroids reportedly may enhance the potassium depletion caused by amphotericin B and should not be used concomitantly unless necessary to control adverse reactions to amphotericin B.

Antineoplastic agents (eg, mechlorethamine) may enhance the potential for renal toxicity, bronchospasm, and hypotension in patients receiving amphotericin B and such concomitant therapy should be used only with great caution.

In a randomized, double-blind study that evaluated use of conventional IV amphotericin B and amphotericin B cholesteryl sulfate complex in febrile neutropenic patients with normal baseline serum creatinine concentrations, the incidence of renal toxicity (defined as a doubling or an increase of 1 mg/dL or more from baseline serum creatinine or a 50% or greater decrease from baseline in calculated creatinine clearance) was 31% in adults and pediatric patients who received amphotericin B cholesteryl sulfate complex concomitantly with cyclosporine or tacrolimus compared with 68% in those who received conventional amphotericin B concomitantly with these agents. In adults and pediatric patients who did not receive cyclosporine or tacrolimus therapy, the incidence of renal toxicity was 8% in those who received amphotericin B cholesteryl sulfate complex and 35% in those who received conventional amphotericin B.

For more Interactions (Complete) data for AMPHOTERICIN B (15 total), please visit the HSDB record page.

Mild and transient elevations in liver enzymes occur in up to 20% of patients receiving amphotericin. Clinically apparent hepatotoxicity is rare, but several convincing cases have been published. The liver injury arises as early as 4 to 14 days after starting therapy, typically with a hepatocellular or mixed pattern of enzyme elevation. Most patients have no symptoms or jaundice. Recovery occurs promptly upon stopping therapy. In addition, isolated but dramatic instances of hyperbilirubinemia arising within days of starting amphotericin have been reported with elevations largely in the direct (conjugated) bilirubin fraction. These patients become visually jaundiced but have no constitutional symptoms, minimal if any elevations in serum ALT or alkaline phosphatase levels, and no evidence of frank hepatic injury. Finally, rare instances of acute cholestatic hepatitis with jaundice have been reported in patients receiving amphotericin, but these patients have generally been critically ill and exposed to multiple potentially hepatotoxic agents, so that the attribution to amphotericin has been weak.

About 80% of the patients will develop infusion-related adverse effects or nephrotoxicity. Amphotericin B interacts with cholesterol in human cell membranes, which is responsible for its toxicity. The common adverse effects of amphotericin B include:

Amphotericin exhibits infusion-related toxicity, which accounts for its extended administration times. Infuse slowly over 3 hours; rapid infusion can cause cardiotoxicity. Amphotericin B deoxycholate overdose can cause ventricular arrhythmias and bradycardia in patients with preexisting cardiac conditions.

/SIGNS AND SYMPTOMS/ Acute overdosage of conventional amphotericin B may result in cardiorespiratory arrest. Adverse cardiovascular effects, including hypotension, bradycardia, and cardiac arrest, have been reported in several pediatric patients who inadvertently received overdosage of conventional amphotericin B.

/SIGNS AND SYMPTOMS/ Four /of 13/ infants had minimal elimination for /amphotericin B/ between doses, a finding that correlates with rises in serum creatinine (greater than 0.4 mg/dL, 40 umol/L) and blood urea nitrogen (greater than 10 mg/dL, 3.6 mmol/L).

/SIGNS AND SYMPTOMS/ Various adverse cardiopulmonary effects, including hypotension, tachypnea, cardiac failure, cardiac arrest, cardiomyopathy, shock, pulmonary edema, hypersensitivity pneumonitis, arrhythmias (including ventricular fibrillation), dyspnea, and hypertension, have been reported in individuals receiving conventional IV amphotericin B.

/SIGNS AND SYMPTOMS/ If severe respiratory distress, anaphylaxis, or an anaphylactoid reaction occurs in a patient receiving amphotericin B, the drug should be discontinued immediately and the patient given appropriate therapy (eg, epinephrine, corticosteroids, maintenance of an adequate airway, oxygen) as indicated.

For more Human Toxicity Excerpts (Complete) data for AMPHOTERICIN B (10 total), please visit the HSDB record page.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Amphotericin B

vLess-DILI-concern

3

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

/LABORATORY ANIMALS: Acute Exposure/ On the corneas of rabbits even 0.0025% /of amphotericin B/ disrupts the epithelial cells, and 1% causes extensive damage to these cells and markedly delays healing of epithelial defects. When more than 5 mg are injected subconjunctivally, a severe local reaction results with permanent yellow discoloration of the conjunctiva and formation of raised nodules that are slow in resolving. Injected into the anterior chamber in rabbits, 0.5 mg severely damaged the corneal endothelium, but 25 ug or 50 ug did not. When injected into the vitreous body in rabbits, some investigators report 5 to 10 ug to be non toxic, while others have reported inflammation, cataract and retinal detachment and necrosis from as little as 1 or 2 ug.[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 96]

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The embryotoxic action of amphotericin B and its methyl derivative was compared in rats after their iv and intraamniotic administration. The concn of amphotericin B and its methyl derivative in the amniotic cavity on days 13, 14 and 15 of pregnancy were 1.5 and 36 ug/mL, respectively. When administered iv during the preimplantation period the antibiotics had no embryotoxic action. Iv administration of amphotericin B in a dose of 500 ug/kg and its derivative in a dose of 2000 ug/kg during organ genesis induced a decrease in the craniocaudal size. In a dose of 3000 ug/kg administered iv the methyl derivative of amphotericin B induced an increase in postimplantation death rates. Administration of amphotericin B to the amniotic cavity had no damaging action. Administration of the methyl derivative on day 15 of pregnancy led to anomalous development of the lower extremities and slower ossification. The threshold doses by the embryotoxic action for iv administration are 500 ug/kg for amphotericin B and 2000 ug/kg for the methyl derivative. Administration of the antibiotics to the amniotic cavity revealed potential teratogenic properties of the amphotericin B methyl derivative.[Moguchenok EA; Antibiot Khimioter 37 (3): 25-8 (1992)]

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Studies in male and female rats using amphotericin B lipid complex at doses up to 0.32 times the usual human dose (based on body surface area) indicate that the drug does not affect fertility. When liposomal amphotericin was administered to rats in 10- or 15-mg/kg doses (equivalent to human doses of 1.6 or 2.4 mg/kg based on body surface area), there was evidence of an abnormal estrous cycle (prolonged diestrus) and decreased number of corpora lutea in female rats receiving the higher dosage but no effect on fertility or days to copulation; there were no effects on male reproductive function.[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 539]

/LABORATORY ANIMALS: Neurotoxicity/ The intracisternal administration of amphotericin B and its mono-methyl ester derivative, via direct intraventricular injection (0.01 to 5 mg/ml, 6 ul) in adult female Wistar rats, revealed that amphotericin B was significantly more toxic than amphotericin B mono-methyl ester, as measured by wt loss, lethargy, death, and central nervous system histopathology. Light and electron microscopy confirmed a greater neurotoxicity for amphotericin B, manifested as edema and modest gliosis extending along and beyond the injection tract. Neuronal degeneration and myelin damage were present in amphotericin B treated (1 mg/mL) animals but were present only modestly in animals treated with amphotericin B mono methyl ester at a fivefold greater concn. Iv administration of amphotericin B to adult female Wistar rats as five daily doses of 5 mg/kg of body wt resulted in significant wt loss and some deaths. Histopathologic examination of the brains, spinal cords, and sural nerves of surviving animals revealed neurotoxicity manifested by neuronal degeneration, gliosis, and myelin edema. In sharp contrast, similar treatment with amphotericin B mono methyl ester at a 10 fold greater dose resulted in neither death nor significant neurotoxicity. The administration of five daily doses of a mixture of amphotericin B mono methyl ester-amphotericin B (9:1; wt/wt) at 50 mg/kg of body wt resulted in neurotoxicity. These results indicate that amphotericin B exhibits significantly greater in vivo neurotoxicity than amphotericin B mono methyl ester.[Reuhl KR et al; Antimicrob Agents Chemother 37 (3): 419-28 (1993)]

For more Non-Human Toxicity Excerpts (Complete) data for AMPHOTERICIN B (6 total), please visit the HSDB record page.

In the event of overdosage with any amphotericin B formulation, therapy with the drug should be discontinued and the patient's clinical status (eg, cardiorespiratory, renal, and liver function, hematologic status, serum electrolytes) monitored. Supportive therapy should be administered as required. ... The patient's condition should be stabilized, including correction of electrolyte abnormalities, prior to reinstituting amphotericin B therapy.

Exchange transfusion may be useful in neonates and infants and should be considered after large iv exposures. In adults, extracorporeal elimination is not expected to be useful because of the drug's low water solubility and high blood-protein binding.

/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/

If severe respiratory distress, anaphylaxis, or an anaphylactoid reaction occurs in a patient receiving amphotericin B, the drug should be discontinued immediately and the patient given appropriate therapy (eg, epinephrine, corticosteroids, maintenance of an adequate airway, oxygen) as indicated.

LD50 Mouse iv 4 mg/kg

LD50 Mouse ip 88 mg/kg

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl amphotericin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

G - Genito urinary system and sex hormones

J - Antiinfectives for systemic use

A - Alimentary tract and metabolism

A - Alimentary tract and metabolism

QA - Alimentary tract and metabolism

QJ - Antiinfectives for systemic use

Amphotericin B shows a high order of <i>in vitro</i> activity against many species of fungi. <i>Histoplasma capsulatum</i>, <i>Coccidioides immitis</i>, <i>Candida species</i>, <i>Blastomyces dermatitidis</i>, <i>Rhodotorula</i>, <i>Cryptococcus neoformans</i>, <i>Sporothrix schenckii</i>, <i>Mucor mucedo</i>, and <i>Aspergillus fumigatus</i> are all inhibited by concentrations of amphotericin B ranging from 0.03 to 1.0 mcg/mL <i>in vitro</i>. While <i>Candida albicans</i> is generally quite susceptible to amphotericin B, non-<i>albicans</i> species may be less susceptible. <i>Pseudallescheria boydii</i> and <i>Fusarium</i> sp. are often resistant to amphotericin B. The antibiotic is without effect on bacteria, rickettsiae, and viruses.

Amphotericin B is fungistatic or fungicidal depending on the concentration obtained in body fluids and the susceptibility of the fungus. The drug acts by binding to sterols (ergosterol) in the cell membrane of susceptible fungi. This creates a transmembrane channel, and the resultant change in membrane permeability allowing leakage of intracellular components. Ergosterol, the principal sterol in the fungal cytoplasmic membrane, is the target site of action of amphotericin B and the azoles. Amphotericin B, a polyene, binds irreversibly to ergosterol, resulting in disruption of membrane integrity and ultimately cell death.

Amphotericin B usually is fungistatic in action at concentrations obtained clinically, but may be fungicidal in high concentrations or against very susceptible organisms. Amphotericin B exerts its antifungal activity principally by binding to sterols (e.g., ergosterol) in the fungal cell membrane. As a result of this binding, the cell membrane is no longer able to function as a selective barrier and leakage of intracellular contents occurs. Cell death occurs in part as a result of permeability changes, but other mechanisms also may contribute to the in vivo antifungal effects of amphotericin B against some fungi. Amphotericin B is not active in vitro against organisms that do not contain sterols in their cell membranes (eg, bacteria).

Binding to sterols in mammalian cells (such as certain kidney cells and erythrocytes) may account for some of the toxicities reported with conventional amphotericin B therapy. At usual therapeutic concentrations of amphotericin B, the drug does not appear to hemolyze mature erythrocytes, and the anemia seen with conventional IV amphotericin B therapy may result from the action of the drug on actively metabolizing and dividing erythropoietic cells.

...Nephrotoxicity associated with conventional IV amphotericin B appears to involve several mechanisms, including a direct vasoconstrictive effect on renal arterioles that reduces glomerular and renal tubular blood flow and a lytic action on cholesterol-rich lysosomal membranes of renal tubular cells. ...

An elimination half-life of approximately 15 days follows an initial plasma half-life of about 24 hours.

Amphotericin B cholesteryl sulfate complex has a distribution half-life of 3.5 minutes and an elimination half-life of 27.5-28.2 hours. /Amphotericin B cholesteryl sulfate complex/

Following IV administration of conventional amphotericin B in patients whose renal function is normal prior to therapy, the initial plasma half-life is approximately 24 hours. After the first 24 hours, the rate at which amphotericin B is eliminated decreases and an elimination half-life of approximately 15 days has been reported.

Elimination, half life: Neonates: Variable (range, 18 to 62.5 hours). Children: Variable (range, 5.5 to 40.3 hours). Adults: Approximately 24 hours. Terminal half life: Approximately 15 days. NOTE: There is large interindividual variation among neonates in the elimination of amphotericin B. Amphotericin B may persist in the circulation of neonates for up to 17 days after it has been discontinued.

. The half life of elimination of amphotericin B from the lungs /of rats/ was 4.8 days according to serial sacrifices done after a single dose of 3.2 mg of aerosol doses of amphotericin B per kg.

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AMPHOTERICIN B

Established Pharmacologic Class [EPC] - Lipid-based Polyene Antifungal

Established Pharmacologic Class [EPC] - Polyene Antifungal

Chemical Structure [CS] - Polyenes

Amphotericin b is a Lipid-based Polyene Antifungal and Polyene Antifungal.

Agents which are destructive to amebae, especially the parasitic species causing AMEBIASIS in man and animal.

Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues.

Substances that are destructive to protozoans.

Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins.

Substances that inhibit the growth or reproduction of BACTERIA.

Bioavailability is 100% for intravenous infusion.

39 +/- 22 mL/hr/kg [febrile neutropenic cancer and bone marrow transplant patients receiving infusion of 1 mg/kg/day at Day 1]

The pharmacokinetics of amphotericin B vary substantially depending on whether the drug is administered as conventional amphotericin B (formulated with sodium desoxycholate), amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, or amphotericin B liposomal, and pharmacokinetic parameters reported for one amphotericin B formulation should not be used to predict the pharmacokinetics of any other amphotericin B formulation.

Amphotericin B is poorly absorbed from the GI tract and must be given parenterally to treat systemic fungal infections. In one study, immediately after completion of iv infusion of 30 mg of amphotericin B (administered over a period of several hours), average peak serum concentrations were about 1 ug/ml; when the dose was 50 mg, average peak serum concentrations were approximately 2 ug/ml. Immediately after infusion, no more than 10% of the amphotericin B dose can be accounted for in serum. Average minimum serum concentrations (recorded just prior to the next drug infusion) of approximately 0.4 ug/ml have been reported when doses of 30 mg were given daily or when doses of 60 mg were given every other day.

Information on the distribution of amphotericin B is limited, although distribution is apparently multicompartmental. The volume of distribution of the drug following administration of conventional amphotericin B has been reported to be 4 L/kg; the volume of distribution at steady state after administration of amphotericin B cholesteryl sulfate is reported to be 3.8-4.1 L/kg. Amphotericin B concentrations attained in inflamed pleura, peritoneum, synovium, and aqueous humor following IV administration of conventional amphotericin B reportedly are about 60% of concurrent plasma concentrations; the drug also is distributed into vitreous humor, pleural, pericardial, peritoneal, and synovial fluid. Amphotericin B reportedly crosses the placenta and low concentrations are attained in amniotic fluid.

Following IV administration of conventional amphotericin B, CSF concentrations of the drug are approximately 3% of concurrent serum concentrations. To achieve fungistatic CSF concentrations, the drug must usually be administered intrathecally. In patients with meningitis, intrathecal administration of 0.2-0.3 mg of conventional amphotericin B via a subcutaneous reservoir has produced peak CSF concentrations of 0.5-0.8 ug/mL; 24 hours after the dose, CSF concentrations were 0.11-0.29 ug/mL. Amphotericin B is removed from the CSF by arachnoid villi and appears to be stored in the extracellular compartment of the brain, which may act as a reservoir for the drug.

MEDICATION

MEDICATION (VET)

Amphotericin B is an antifungal antibiotic produced from a strain of Streptomyces nodosus.

THERAP CAT: Antifungal

Very high concentrations of amphotericin B increase the permeability of the sarcolemmal membrane, and electrophysiologists use the drug to create perforated patch-clamp models.

Use (kg; approx.) in Germany (2009): >1000

(1977) PROBABLY GREATER THAN 9.08X10+5 GRAMS

(1979) PROBABLY GREATER THAN 9.08X10+5 GRAMS

Dutcher et al., US patent 2,908,611 (1959 to Olin Mathieson)

Fermentation of Streptomyces nodosus cultures

MYSTECLIN-F /SRP: TETRACYCLINE-AMPHOTERICIN B COMBINATION/.

Amphotericin B is ... formulated for iv infusion by complexing it with the bile salt deoxycholate ... /and/ marketed as a lyophilized powder (FUNGIZONE) containing 50 mg of amphotericin B, 41 mg of deoxycholate, and a small amount of sodium phosphate buffer. The amphotericin B-deoxycholate complex (DOC) forms a colloid in water ... N-acyl and O-acyl derivatives of amphotericin B form water-soluble salts, but none is available commercially.

... /Three/ lipid formulations for iv infusion /are available/. Amphotericin B colloidal dispersion (ABCD, AMPHOTEC, AMPHOCIL) ... /contains/ roughly equimolar amounts of amphotericin B and cholesteryl sulfate ... /In/ a unilamellar vesicle formulation ... (AMBISOME) ... amphotericin B (50 mg) is combined with 350 mg of lipid in an approximately 10% molar ratio. The lipid contains hydrogenated soy lecithin (phosphatidylcholine), cholesterol, and distearoylphosphatidylglycerol in a 10:5:4 molar ratio. The drug is supplied as a lyophilized powder, which is reconstituted with sterile water for injection and then the dose diluted with 5% dextrose solution ... The third lipid formulation is amphotericin B lipid complex (ABLC, ABELCET). This preparation of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol in a 7:3 mixture with approximately 35 mol% amphotericin B forms ribbon-like sheets ...

The amphotericin B-deoxycholate complex (DOC) has been mixed with a 20% lipid emulsion (INTRALIPID) ...

For more Formulations/Preparations (Complete) data for AMPHOTERICIN B (10 total), please visit the HSDB record page.

Polyene antibiotic produced by Streptomycetes nodosus M4575 obtained from soil of the Orinoco river region of Venezuela.

Commercially available as a deoxycholate complex.

Amphotericin B was found in the mycelium of Streptomyces nodosus M-4575 by Gold et al. of the Squibb Institute of Medical Research in 1956. It is produced with another polyene macrolide antibiotic, amphotericin A, and separated by solvent extraction.