166663-25-8 Usage
Uses
Used in Pharmaceutical Industry:
Anidulafungin is used as an intravenous treatment for serious fungal infections, such as candidemia, Candida-derived peritonitis, intra-abdominal abscesses, and esophageal candidiasis. Its potent action and lack of significant drug interactions make it a preferred choice for treating invasive candidiasis.
Used in Antifungal Therapy:
Anidulafungin is used as an antifungal agent for the treatment of invasive candidiasis caused by susceptible Candida species. Its unique mode of action, targeting the cell wall synthesis, helps in overcoming the rising resistance to azole and amphotericin B antifungals, with no cross-resistance expected.
Brand Name:
Anidulafungin is commercially known as Eraxis (Vicuron) and was developed and launched by Eli Lilly.
Antimicrobial activity
It is active against Aspergillus spp., Candida spp. and the cyst
stage of Pneumocystis jirovecii. Resistance has not yet been
reported.
Pharmaceutical Applications
A semisynthetic lipopeptide derived from a fermentation
product of Aspergillus nidulans. Formulated for intravenous
infusion.
Pharmacokinetics
Cmax 100 mg 1-h infusion: c. 9 mg/L end infusion
Plasma half-life: 18–27 h
Volume of distribution: 0.6 L/kg
Plasma protein binding: 84%
Blood concentrations increase in proportion to dosage. The
steady state is achieved on the first day after a loading dose
(twice the daily maintenance dose).
Distribution
Levels in the CSF are negligible.
Metabolism and excretion
Unlike caspofungin and micafungin, anidulafungin is not metabolized by the liver, but undergoes slow non-enzymatic degradation in the blood to a peptide breakdown product which is enzymatically degraded and excreted in the feces and bile. About 30% of a dose is eliminated in the feces, of which less than 10% is unchanged drug. Less than 1% of a dose is excreted in the urine. No dosage adjustment is required in patients with hepatic or renal impairment. Anidulafungin is not cleared by hemodialysis.
Clinical Use
Candidemia and certain invasive forms of candidosis
Esophageal candidosis
Side effects
Occasional histamine-mediated infusion-related reactions,
injection site reactions and transient abnormalities of liver
enzymes have been reported.
Drug interactions
Potentially hazardous interactions with other drugs
None known
Metabolism
Hepatic metabolism of anidulafungin has not been
observed. Anidulafungin is not a clinically relevant
substrate, inducer, or inhibitor of cytochrome P450
isoenzymes.
Anidulafungin undergoes slow chemical degradation at
physiologic temperature and pH to a ring-opened peptide
that lacks antifungal activity. The ring-opened product
is subsequently converted to peptidic degradants and
eliminated mainly through biliary excretion.
In a single-dose clinical study, radiolabelled
[14C]-anidulafungin (~88 mg) was administered to
healthy subjects. Approximately 30% of the administered
radioactive dose was eliminated in the faeces over 9 days,
of which less than 10% was intact drug. Less than 1%
of the administered radioactive dose was excreted in the
urine, indicating negligible renal clearance.
references
[1] zhanel gg1, karlowsky ja, harding ga, balko tv, zelenitsky sa, friesen m, kabani a, turik m, hoban dj. in vitro activity of a new semisynthetic echinocandin, ly-303366, against systemic isolates of candida species, cryptococcus neoformans, blastomyces dermatitidis, and aspergillus species. antimicrob agents chemother. 1997 apr;41(4):863-5.
Check Digit Verification of cas no
The CAS Registry Mumber 166663-25-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,6,6,6,6 and 3 respectively; the second part has 2 digits, 2 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 166663-25:
(8*1)+(7*6)+(6*6)+(5*6)+(4*6)+(3*3)+(2*2)+(1*5)=158
158 % 10 = 8
So 166663-25-8 is a valid CAS Registry Number.
InChI:InChI=1/C58H73N7O17/c1-5-6-7-24-82-40-22-18-35(19-23-40)33-10-8-32(9-11-33)34-12-14-37(15-13-34)51(74)59-41-26-43(70)54(77)63-56(79)47-48(71)29(2)27-65(47)58(81)45(31(4)67)61-55(78)46(50(73)49(72)36-16-20-38(68)21-17-36)62-53(76)42-25-39(69)28-64(42)57(80)44(30(3)66)60-52(41)75/h8-23,29-31,39,41-50,54,66-73,77H,5-7,24-28H2,1-4H3,(H,59,74)(H,60,75)(H,61,78)(H,62,76)(H,63,79)/t29-,30+,31+,39+,41-,42-,43+,44-,45-,46-,47-,48-,49-,50-,54+/m0/s1
166663-25-8Relevant articles and documents
Commercialization and late-stage development of a semisynthetic antifungal API: Anidulafungin/D-fructose (eraxis)
Norris, Timothy,VanAlsten, John,Hubbs, Stephen,Ewing, Marcus,Cai, Weiling,Jorgensen, Matthew L.,Bordner, Jon,Jensen, Grace O.
, p. 447 - 455 (2008)
Many years ago anidulafungin 1 was identified as a potentially useful medicine for the treatment of fungal infections. Its chemical and physical properties as a relatively high molecular weight semisynthetic derived from echinocandin B proved to be a significant hurdle to its final presentation as a useful medicine. It has recently been approved as an intravenous treatment for invasive candidaisis, an increasingly common health hazard that is potentially life-threatening. The development and commercialization of this API, which is presented as a molecular mixture of anidulafungin and D-fructose is described. This includes, single crystal X-ray structures of the starting materials, the echinocandin B cyclic-peptide nucleus (ECBN · HCI) and the active ester 1-({[4 - (pentyloxy)-1,1 :4,1-terphenyl-4-yl]carbonyl}oxy)-1H-1,2,3- benzotriazole (TOBt). Details of the structure and properties of starting materials, scale-up chemistry and unusual crystallization phenomena associated with the API formation are discussed.
Semisynthetic Chemical Modification of the Antifungal Lipopeptide Echinocandin B (ECB): Structure-Activity Studies of the Lipophilic and Geometric Parameters of Polyarylated Acyl Analogs of ECB
Debono, Manuel,Turner, William W.,LaGrandeur, Lisa,Burkhadt, Fred J.,Nissen , Jeffrey S.,et al.
, p. 3271 - 3281 (2007/10/02)
Echinocandin B (ECB) is a lipopeptide composed of a complex cyclic peptide acylated at the N-terminus by linoleic acid.Enzymatic deacylation of ECB provided the peptide "nucleus" as a biologically inactive substrate from which novel ECB analogs were generated by chemical reacylation at the N-terminus.Varying the acyl group revealed that the structure and physical properties of the side chain, particularly its geometry and lipophlicity, played a pivotal role in determining the antifungal potency properties of the analog.Using CLOGP values to describe and compare the lipophlicities of the side chain fragments, it was shown that values of >3.5 were required for expression of antifungal activity.Sercondly, a linearly rigid geometry of the side chain was the most effective shape in enhancing the antifungal potency.Using these parameters as a guide, a variety of novel ECB analogs were synthesized which included arylacyl groups that incorporated biphenyl, terphenyl, tetraphenyl, and arylethynyl groups.Generally the glucan synthase inhibition by these analogs correlated well with in vitro and in vivo activities and was likewise influenced by the structure of the side chain.These structural variations resulted in enhancement of antifungal activity in both in vitro and in vivo assays.Some of these analogs, including LY303336 (14a), were effective by the oral route of administartion.
