Identification

Name
Micafungin
Accession Number
DB01141  (APRD01114)
Type
Small Molecule
Groups
Approved, Investigational
Description

Micafungin is an antifungal drug. It belongs to the antifungal class of compounds known as echinocandins and exerts its effect by inhibiting the synthesis of 1,3-beta-D-glucan, an integral component of the fungal cell wall.

Structure
Thumb
Synonyms
Not Available
External IDs
FK-463
Product Ingredients
IngredientUNIICASInChI Key
Micafungin sodiumIS1UP79R56208538-73-2KOOAFHGJVIVFMZ-WZPXRXMFSA-M
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MycamineInjection, powder, lyophilized, for solution20 mg/1mLIntravenousAstellas Pharma Inc2014-12-01Not applicableUs
MycaminePowder, for solution50 mgIntravenousAstellas Pharma Inc2007-09-18Not applicableCanada
MycamineInjection, powder, lyophilized, for solution10 mg/1mLIntravenousAstellas Pharma Inc2014-12-01Not applicableUs
MycaminePowder, for solution100 mgIntravenousAstellas Pharma Inc2009-12-17Not applicableCanada
International/Other Brands
Mycamine
Categories
UNII
R10H71BSWG
CAS number
235114-32-6
Weight
Average: 1270.274
Monoisotopic: 1269.438350313
Chemical Formula
C56H71N9O23S
InChI Key
PIEUQSKUWLMALL-YABMTYFHSA-N
InChI
InChI=1S/C56H71N9O23S/c1-4-5-6-17-86-32-14-11-28(12-15-32)39-21-33(63-87-39)27-7-9-29(10-8-27)49(75)58-34-20-38(70)52(78)62-54(80)45-46(72)25(2)23-65(45)56(82)43(37(69)22-41(57)71)60-53(79)44(48(74)47(73)30-13-16-36(68)40(18-30)88-89(83,84)85)61-51(77)35-19-31(67)24-64(35)55(81)42(26(3)66)59-50(34)76/h7-16,18,21,25-26,31,34-35,37-38,42-48,52,66-70,72-74,78H,4-6,17,19-20,22-24H2,1-3H3,(H2,57,71)(H,58,75)(H,59,76)(H,60,79)(H,61,77)(H,62,80)(H,83,84,85)/t25-,26+,31+,34-,35-,37+,38+,42-,43-,44-,45-,46-,47-,48-,52+/m0/s1
IUPAC Name
{5-[(1S,2S)-2-[(3S,6S,9S,11R,15S,18S,20R,21R,24S,25S,26S)-3-[(1R)-2-carbamoyl-1-hydroxyethyl]-11,20,21,25-tetrahydroxy-15-[(1R)-1-hydroxyethyl]-26-methyl-2,5,8,14,17,23-hexaoxo-18-(4-{5-[4-(pentyloxy)phenyl]-1,2-oxazol-3-yl}benzamido)-1,4,7,13,16,22-hexaazatricyclo[22.3.0.0⁹,¹³]heptacosan-6-yl]-1,2-dihydroxyethyl]-2-hydroxyphenyl}oxidanesulfonic acid
SMILES
CCCCCOC1=CC=C(C=C1)C1=CC(=NO1)C1=CC=C(C=C1)C(=O)N[C@H]1C[C@@H](O)[C@@H](O)NC(=O)[C@@H]2[C@@H](O)[C@@H](C)CN2C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC1=O)[C@@H](C)O)[C@H](O)[C@@H](O)C1=CC(OS(O)(=O)=O)=C(O)C=C1)[C@H](O)CC(N)=O

Pharmacology

Indication

For use in the treatment of candidemia, acute disseminated candidiasis, and certain other invasive Candida infections, as well as esophageal candidiasis, and prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation. Micafungin is also used as an alternative for the treatment of oropharyngeal candidiases and has been used with some success as primary or salvage therapy, alone or in combination with other antifungals, for the treatment of invasive aspergillosis.

Associated Conditions
Pharmacodynamics

Formerly known as FK463, micafungin is a semisynthetic lipopeptide synthesized from a fermentation product of Coleophoma empetri that works as an antifungal agent. It is a glucan synthesis inhibitor of the echinocandin structural class. The U.S. Food and Drug Administration approved micafungin in March 2005. Micafungin inhibits an enzyme essential for fungal cell-wall synthesis. Depending on its concentration, micafungin may be fungicidal against some Candida, but is usually fungistatic against Apergillus. Micafungin can be used concomitantly with a variety of other drugs, including the HIV protease inhibitor ritonavir and the transplant medications cyclosporine and tacrolimus.

Mechanism of action

Micafungin inhibits the synthesis of beta-1,3-D-glucan, an essential component of fungal cell walls which is not present in mammalian cells. It does this by inhibiting beta-1,3-D-glucan synthase.

TargetActionsOrganism
A1,3-beta-glucan synthase component FKS1
inhibitor
Aspergillus niger (strain CBS 513.88 / FGSC A1513)
Absorption

Not absorbed orally

Volume of distribution
  • 0.39 ± 0.11 L/kg [adult patients with esophageal candidiasis]
Protein binding

Highly (>99%) protein bound in vitro, independent of plasma concentrations over the range of 10 to 100 µg/mL. The primary binding protein is albumin; however, micafungin, at therapeutically relevant concentrations, does not competitively displace bilirubin binding to albumin. Micafungin also binds to a lesser extent to a1-acid-glycoprotein.

Metabolism

Micafungin is metabolized to M-1 (catechol form) by arylsulfatase, with further metabolism to M-2 (methoxy form) by catechol-O-methyltransferase. M-5 is formed by hydroxylation at the side chain (w-1 position) of micafungin catalyzed by cytochrome P450 (CYP) isozymes. Even though micafungin is a substrate for and a weak inhibitor of CYP3A in vitro, hydroxylation by CYP3A is not a major pathway for micafungin metabolism in vivo.

Route of elimination

Fecal excretion is the major route of elimination (total radioactivity at 28 days was 71% of the administered dose).

Half life

14-17 hours

Clearance
  • 0.359 +/- 0.179 mL/min/kg [Adult Patients with IC with 100 mg]
  • 0.321 +/- 0.098 mL/min/kg [HIV- Positive Patients with EC with 50 mg]
  • 0.327 +/- 0.093 mL/min/kg [HIV- Positive Patients with EC with 100 mg]
  • 0.340 +/- 0.092 mL/min/kg [HIV- Positive Patients with EC with 150 mg]
  • 0.214 +/- 0.031 mL/min/kg [hematopoietic stem cell transplant recipients 3 mg/kg]
  • 0.204 +/- 0.036 mL/min/kg [hematopoietic stem cell transplant recipients 4 mg/kg]
  • 0.224 +/- 0.064 mL/min/kg [hematopoietic stem cell transplant recipients 6 mg/kg]
  • 0.223 +/- 0.081 mL/min/kg [hematopoietic stem cell transplant recipients 8 mg/kg]
Toxicity

Intravenous LD50 in rats is 125mg/kg. In dogs it is >200mg/kg. No cases of overdosage have been reported. Repeated daily doses up to 8 mg/kg (maximum total dose of 896 mg) in adult patients have been administered in clinical trials with no reported dose-limiting toxicity. The minimum lethal dose is 125 mg/kg in rats, equivalent to 8.1 times the recommended human clinical dose for esophageal candidiasis based on body surface area comparisons.

Affected organisms
  • Aspergillis, Candida and other fungi
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
Amphotericin BThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Micafungin.
AmrinoneThe therapeutic efficacy of Micafungin can be increased when used in combination with Amrinone.
AzimilideThe therapeutic efficacy of Micafungin can be increased when used in combination with Azimilide.
BuspironeThe metabolism of Buspirone can be decreased when combined with Micafungin.
BusulfanThe serum concentration of Busulfan can be increased when it is combined with Micafungin.
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Micafungin.
DidanosineDidanosine can cause a decrease in the absorption of Micafungin resulting in a reduced serum concentration and potentially a decrease in efficacy.
DocetaxelThe metabolism of Docetaxel can be decreased when combined with Micafungin.
EntacaponeThe metabolism of Micafungin can be decreased when combined with Entacapone.
EtravirineThe serum concentration of Etravirine can be increased when it is combined with Micafungin.
Food Interactions
Not Available

References

General References
  1. Grover ND: Echinocandins: A ray of hope in antifungal drug therapy. Indian J Pharmacol. 2010 Feb;42(1):9-11. doi: 10.4103/0253-7613.62396. [PubMed:20606829]
  2. Bormann AM, Morrison VA: Review of the pharmacology and clinical studies of micafungin. Drug Des Devel Ther. 2009 Dec 29;3:295-302. [PubMed:20054447]
  3. Vehreschild JJ, Cornely OA: Micafungin sodium, the second of the echinocandin class of antifungals: theory and practice. Future Microbiol. 2006 Aug;1(2):161-70. [PubMed:17661660]
  4. Groll AH, Stergiopoulou T, Roilides E, Walsh TJ: Micafungin: pharmacology, experimental therapeutics and clinical applications. Expert Opin Investig Drugs. 2005 Apr;14(4):489-509. [PubMed:15882123]
  5. Chandrasekar PH, Sobel JD: Micafungin: a new echinocandin. Clin Infect Dis. 2006 Apr 15;42(8):1171-8. Epub 2006 Mar 14. [PubMed:16575738]
  6. Wiederhold NP, Lewis JS 2nd: The echinocandin micafungin: a review of the pharmacology, spectrum of activity, clinical efficacy and safety. Expert Opin Pharmacother. 2007 Jun;8(8):1155-66. [PubMed:17516879]
  7. Ikeda F, Tanaka S, Ohki H, Matsumoto S, Maki K, Katashima M, Barrett D, Aoki Y: Role of micafungin in the antifungal armamentarium. Curr Med Chem. 2007;14(11):1263-75. [PubMed:17504145]
  8. Sucher AJ, Chahine EB, Balcer HE: Echinocandins: the newest class of antifungals. Ann Pharmacother. 2009 Oct;43(10):1647-57. doi: 10.1345/aph.1M237. Epub 2009 Sep 1. [PubMed:19724014]
  9. Morris MI, Villmann M: Echinocandins in the management of invasive fungal infections, part 1. Am J Health Syst Pharm. 2006 Sep 15;63(18):1693-703. [PubMed:16960253]
  10. Morris MI, Villmann M: Echinocandins in the management of invasive fungal infections, Part 2. Am J Health Syst Pharm. 2006 Oct 1;63(19):1813-20. [PubMed:16990627]
External Links
Human Metabolome Database
HMDB0015272
KEGG Drug
D02465
KEGG Compound
C15819
PubChem Compound
477468
PubChem Substance
46508208
ChemSpider
419105
ChEBI
600520
ChEMBL
CHEMBL457547
Therapeutic Targets Database
DAP000548
PharmGKB
PA164781026
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Micafungin
ATC Codes
J02AX05 — Micafungin
AHFS Codes
  • 08:14.16 — Echinocandins
FDA label
Download (139 KB)
MSDS
Download (84.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableCandidemia / Candidiasis, Invasive / Esophageal Candidiasis / Oropharyngeal Candidiasis1
1CompletedNot AvailableProphylaxis of Candida Infections1
1CompletedBasic ScienceInfections, Fungal1
1CompletedOtherCandidemia / Candidiasis, Invasive / Esophageal Candidiasis / Oropharyngeal Candidiasis1
1CompletedPreventionInfections, Fungal1
1RecruitingTreatmentCandidiasis, Invasive1
1SuspendedTreatmentPrimary Central Nervious System Lymphoma1
1TerminatedBasic ScienceBone Marrow Transplant (BMT) / Cancers / Immunocompromised1
2CompletedOtherAcute Graft Versus Host Disease Grade II-IV / Allogeneic Stem Cell Transplant / Leukemia Acute Myeloid Leukemia (AML) / Myelo Dysplastic Syndrome1
2CompletedPreventionLeukemia, Acute1
2CompletedPreventionMycoses1
2CompletedTreatmentCandida Meningitis / Candidiasis, Systemic1
2CompletedTreatmentCandidemia / Candidiasis, Invasive / Mycoses1
2CompletedTreatmentHematological Diseases / Neutropenia, Febrile1
2CompletedTreatmentInvasive Fungal Infections1
2TerminatedTreatmentAspergillosis1
2TerminatedTreatmentInvasive Aspergillosis1
2Unknown StatusPreventionFungal Diseases / Neutropenias1
2WithdrawnTreatmentAspergillosis1
2, 3Not Yet RecruitingTreatmentCandidiasis infection1
3CompletedPreventionFungaemia / Infections, Fungal1
3CompletedPreventionMycoses / Transplantation, Liver1
3CompletedTreatmentCandidemia / Candidiasis, Invasive1
3CompletedTreatmentCandidemia / Candidiasis infection1
3CompletedTreatmentCandidiasis, Invasive1
3CompletedTreatmentInfections, Fungal1
3CompletedTreatmentOral Candidiasis2
3CompletedTreatmentCandidiasis infection1
3TerminatedPreventionInvasive Fungal Infections1
3TerminatedTreatmentCandidiasis infection1
3Unknown StatusPreventionLiver Transplant Recipients1
4CompletedBasic ScienceObesity, Morbid1
4CompletedTreatmentAcute Myelogenous Leukaemia (AML) / Myelodysplastic Syndrome1
4CompletedTreatmentBMI >27 kg/m2 / BMI >30 kg/m2 / Nutrition Disorders1
4CompletedTreatmentCandida Sepsis1
4CompletedTreatmentCandidemia1
4TerminatedTreatmentAspergillosis / Candidiasis infection1
4TerminatedTreatmentCandidemia / Candidiasis infection1
4TerminatedTreatmentInvasive Aspergillosis1
4Unknown StatusPreventionHematopoietic Stem Cell Transplantation (HSCT) / Invasive Fungal Disease / Neutropenias1
4WithdrawnTreatmentAspergillosis/Blood / Aspergillosis/Invasive1
4WithdrawnTreatmentCandidiasis infection / Sepsis1
Not AvailableCompletedNot AvailableHaemopathy / Prophylaxis of moderate Pneumocystis pneumonia1
Not AvailableCompletedNot AvailableInvasive Fungal Infections3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Astellas Pharma Inc.
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous10 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous20 mg/1mL
Powder, for solutionIntravenous100 mg
Powder, for solutionIntravenous50 mg
Prices
Unit descriptionCostUnit
Mycamine 100 mg vial224.4USD vial
Mycamine 50 mg vial112.2USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5376634No1994-12-272011-12-27Us
CA2202058No2007-11-062015-09-29Canada
CA2044746No2001-08-072011-06-17Canada
US6107458No1999-03-162019-03-16Us
US6265536No1995-09-292015-09-29Us
US6774104No2001-01-082021-01-08Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityFreely soluble as sodium salt (> 200mg/mL)Not Available
logP-1.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.218 mg/mLALOGPS
logP0.67ALOGPS
logP-6.3ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)-2.2ChemAxon
pKa (Strongest Basic)-3.6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count22ChemAxon
Hydrogen Donor Count16ChemAxon
Polar Surface Area510.14 Å2ChemAxon
Rotatable Bond Count18ChemAxon
Refractivity303.07 m3·mol-1ChemAxon
Polarizability128.22 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8383
Blood Brain Barrier-0.8524
Caco-2 permeable-0.6464
P-glycoprotein substrateSubstrate0.7906
P-glycoprotein inhibitor INon-inhibitor0.6752
P-glycoprotein inhibitor IINon-inhibitor0.9279
Renal organic cation transporterNon-inhibitor0.9428
CYP450 2C9 substrateNon-substrate0.8485
CYP450 2D6 substrateNon-substrate0.7911
CYP450 3A4 substrateSubstrate0.5853
CYP450 1A2 substrateNon-inhibitor0.7414
CYP450 2C9 inhibitorNon-inhibitor0.7017
CYP450 2D6 inhibitorNon-inhibitor0.8251
CYP450 2C19 inhibitorNon-inhibitor0.693
CYP450 3A4 inhibitorInhibitor0.5393
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7703
Ames testNon AMES toxic0.563
CarcinogenicityCarcinogens 0.5763
BiodegradationNot ready biodegradable0.9916
Rat acute toxicity2.5651 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9686
hERG inhibition (predictor II)Inhibitor0.716
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Oligopeptides
Alternative Parents
Cyclic peptides / Macrolactams / N-acyl-alpha amino acids and derivatives / Phenylsulfates / Benzamides / Benzoyl derivatives / Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / 1-hydroxy-2-unsubstituted benzenoids
show 19 more
Substituents
Alpha-oligopeptide / Cyclic alpha peptide / Macrolactam / N-acyl-alpha amino acid or derivatives / Phenylsulfate / Alpha-amino acid or derivatives / Arylsulfate / Benzamide / Benzoic acid or derivatives / Phenoxy compound
show 40 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
antibiotic antifungal drug, echinocandin (CHEBI:600520)

Targets

Kind
Protein
Organism
Aspergillus niger (strain CBS 513.88 / FGSC A1513)
Pharmacological action
Yes
Actions
Inhibitor
General Function
1,3-beta-d-glucan synthase activity
Specific Function
Catalytic subunit of the 1,3-beta-glucan synthase. Synthesizes 1,3-beta-glucan, a major structural component of the cell wall. Involved in cell wall synthesis, maintenance and cell wall remodeling ...
Gene Name
fksA
Uniprot ID
A2QLK4
Uniprot Name
1,3-beta-glucan synthase component FKS1
Molecular Weight
216972.8 Da
References
  1. Sucher AJ, Chahine EB, Balcer HE: Echinocandins: the newest class of antifungals. Ann Pharmacother. 2009 Oct;43(10):1647-57. doi: 10.1345/aph.1M237. Epub 2009 Sep 1. [PubMed:19724014]
  2. Quindos G, Eraso E, Javier Carrillo-Munoz A, Canton E, Peman J: [In vitro antifungal activity of micafungin]. Rev Iberoam Micol. 2009 Mar 31;26(1):35-41. doi: 10.1016/S1130-1406(09)70006-3. Epub 2009 May 7. [PubMed:19463275]
  3. Morris MI, Villmann M: Echinocandins in the management of invasive fungal infections, part 1. Am J Health Syst Pharm. 2006 Sep 15;63(18):1693-703. [PubMed:16960253]
  4. Morris MI, Villmann M: Echinocandins in the management of invasive fungal infections, Part 2. Am J Health Syst Pharm. 2006 Oct 1;63(19):1813-20. [PubMed:16990627]
  5. Jarvis B, Figgitt DP, Scott LJ: Micafungin. Drugs. 2004;64(9):969-82; discussion 983-4. [PubMed:15101786]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
O-methyltransferase activity
Specific Function
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOP...
Gene Name
COMT
Uniprot ID
P21964
Uniprot Name
Catechol O-methyltransferase
Molecular Weight
30036.77 Da
References
  1. Groll AH, Stergiopoulou T, Roilides E, Walsh TJ: Micafungin: pharmacology, experimental therapeutics and clinical applications. Expert Opin Investig Drugs. 2005 Apr;14(4):489-509. [PubMed:15882123]
  2. Wiederhold NP, Lewis JS 2nd: The echinocandin micafungin: a review of the pharmacology, spectrum of activity, clinical efficacy and safety. Expert Opin Pharmacother. 2007 Jun;8(8):1155-66. [PubMed:17516879]
  3. Julius JM, Gaikwad A, Lowry A, Lewis RE, Lozano RD, Dalrymple JL, Coleman RL, Smith JA: Defining the role of echinocandin catechol functional groups in the development of secondary hepatocellular carcinoma. J Antimicrob Chemother. 2012 Feb;67(2):422-9. doi: 10.1093/jac/dkr494. Epub 2011 Nov 30. [PubMed:22129592]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sulfuric ester hydrolase activity
Specific Function
Hydrolyzes cerebroside sulfate.
Gene Name
ARSA
Uniprot ID
P15289
Uniprot Name
Arylsulfatase A
Molecular Weight
53587.6 Da
References
  1. Groll AH, Stergiopoulou T, Roilides E, Walsh TJ: Micafungin: pharmacology, experimental therapeutics and clinical applications. Expert Opin Investig Drugs. 2005 Apr;14(4):489-509. [PubMed:15882123]
  2. Wiederhold NP, Lewis JS 2nd: The echinocandin micafungin: a review of the pharmacology, spectrum of activity, clinical efficacy and safety. Expert Opin Pharmacother. 2007 Jun;8(8):1155-66. [PubMed:17516879]

Drug created on June 13, 2005 07:24 / Updated on September 18, 2018 23:02