Micafungin

Các tên gọi khác (1) :

Mycamine

antifungal agents

Thuốc Gốc

Small Molecule

CAS: 235114-32-6

ATC: J02AX05

ĐG : Astellas Pharma Inc. , http://www.astellas.com

CTHH: C₅₆H₇₁N₉O₂₃S

PTK: 1270.274

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.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₅₆H₇₁N₉O₂₃S

Phân tử khối

1270.274

Monoisotopic mass

1269.438350313

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

InChI Key

InChIKey=PIEUQSKUWLMALL-YABMTYFHSA-N

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}benzene)amido]-1,4,7,13,16,22-hexaazatricyclo[22.3.0.0^{9,13}]heptacosan-6-yl]-1,2-dihydroxyethyl]-2-hydroxyphenyl}oxidanesulfonic acid

Traditional 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[22.3.0.0^{9,13}]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

Độ hòa tan

Freely soluble as sodium salt (> 200mg/mL)

logP

-1.5

logS

-3.8

pKa (strongest acidic)

-2.2

pKa (Strongest Basic)

-3.6

PSA

510.14 Å²

Refractivity

303.07 m³·mol^-1

Polarizability

128.22 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

-1

Number of Rings

Bioavailability

MDDR-Like Rule

true

Dược Lực Học : 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.

Cơ Chế Tác Dụng : 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. 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.

Dược Động Học :

▧ 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]

Độc Tính : 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.

Chỉ Định : 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.

Liều Lượng & Cách Dùng : Injection, powder, lyophilized, for solution - Intravenous drip - 100 mg
Injection, powder, lyophilized, for solution - Intravenous drip - 50 mg

Dữ Kiện Thương Mại

Giá thị trường

Biệt dược thương mại : Mycamine 50 mg vial

Giá bán buôn : USD >112.2

Đơn vị tính : vial
Biệt dược thương mại : Mycamine 100 mg vial

Giá bán buôn : USD >224.4

Đơn vị tính : vial

Nhà Sản Xuất

Công ty :

Sản phẩm biệt dược : Mycamine

Đóng gói

Công ty : Astellas Pharma Inc.

Website : http://www.astellas.com

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB01141

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=477468

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508208

KEGG Compound

http://www.genome.jp/dbget-bin/www_bget?cpd:C15819

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D02465

ChemSpider

http://www.chemspider.com/Chemical-Structure.2339421.html

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0469-3250-10

PharmGKB

http://www.pharmgkb.org/drug/PA164781026

Wikipedia

http://en.wikipedia.org/wiki/Micafungin

RxList

http://www.rxlist.com/cgi/generic4/mycamine.htm

Drugs.com

http://www.drugs.com/cdi/micafungin.html

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