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Details

Stereochemistry ABSOLUTE
Molecular Formula C37H42F2N8O4
Molecular Weight 700.7774
Optical Activity ( - )
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of POSACONAZOLE

SMILES

CC[C@@H]([C@H](C)O)N1N=CN(C1=O)C2=CC=C(C=C2)N3CCN(CC3)C4=CC=C(OC[C@@H]5CO[C@](CN6C=NC=N6)(C5)C7=CC=C(F)C=C7F)C=C4

InChI

InChIKey=RAGOYPUPXAKGKH-XAKZXMRKSA-N
InChI=1S/C37H42F2N8O4/c1-3-35(26(2)48)47-36(49)46(25-42-47)31-7-5-29(6-8-31)43-14-16-44(17-15-43)30-9-11-32(12-10-30)50-20-27-19-37(51-21-27,22-45-24-40-23-41-45)33-13-4-28(38)18-34(33)39/h4-13,18,23-27,35,48H,3,14-17,19-22H2,1-2H3/t26-,27+,35-,37-/m0/s1

HIDE SMILES / InChI

Description

Posaconazole is a triazole antifungal drug that is used to treat invasive infections by Candida species and Aspergillus species in severely immunocompromised patients. It marketed in the United States, the European Union, and in other countries by Schering-Plough under the trade name Noxafil. Noxafil is used for prophylaxis of invasive Aspergillus and Candida infections in patients, 13 years of age and older, who are at high risk of developing these infections due to being severely immunocompromised as a result of procedures such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD), or due to hematologic malignancies with prolonged neutropenia from chemotherapy. Also for the treatment of oropharyngeal candidiasis, including oropharyngeal candidiasis refractory to itraconazole and/or fluconazole. Posaconazole blocks the synthesis of ergosterol, a key component of the fungal cell membrane, through the inhibition of cytochrome P-450 dependent enzyme lanosterol 14α-demethylase responsible for the conversion of lanosterol to ergosterol in the fungal cell membrane. This results in an accumulation of methylated sterol precursors and a depletion of ergosterol within the cell membrane thus weakening the structure and function of the fungal cell membrane. This may be responsible for the antifungal activity of posaconazole. It is absorbed within three to five hours and predominately eliminated through the liver, and has a half-life of about 35 hours. Oral administration of posaconazole taken with a high-fat meal exceeds 90% bioavailability and increases the concentration by four times compared to fasting state.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
25.0 nM [Kd]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
NOXAFIL
Preventing
NOXAFIL
Curative
NOXAFIL

Cmax

ValueDoseCo-administeredAnalytePopulation
2764 ng/mL
300 mg single, oral
[NO STEREO] POSACONAZOLE plasma
Homo sapiens
935 ng/mL
300 mg single, oral
[NO STEREO] POSACONAZOLE plasma
Homo sapiens
1060 ng/mL
300 mg single, oral
[NO STEREO] POSACONAZOLE plasma
Homo sapiens
2840 ng/mL
300 mg single, intravenous
[NO STEREO] POSACONAZOLE plasma
Homo sapiens
3280 ng/mL
300 mg 1 times / day multiple, intravenous
POSACONAZOLE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
9093 ng × h/mL
400 mg 2 times / day steady-state, oral
[NO STEREO] POSACONAZOLE plasma
Homo sapiens
51618 ng × h/mL
300 mg single, oral
[NO STEREO] POSACONAZOLE plasma
Homo sapiens
26200 ng × h/mL
300 mg single, oral
[NO STEREO] POSACONAZOLE plasma
Homo sapiens
38400 ng × h/mL
300 mg single, oral
[NO STEREO] POSACONAZOLE plasma
Homo sapiens
46400 ng × h/mL
300 mg single, intravenous
[NO STEREO] POSACONAZOLE plasma
Homo sapiens
36100 ng × h/mL
300 mg 1 times / day multiple, intravenous
POSACONAZOLE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
31.7 h
400 mg 2 times / day steady-state, oral
[NO STEREO] POSACONAZOLE plasma
Homo sapiens
31 h
300 mg single, oral
[NO STEREO] POSACONAZOLE plasma
Homo sapiens
24.6 h
300 mg single, intravenous
[NO STEREO] POSACONAZOLE plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
300 mg single, intravenous
[NO STEREO] POSACONAZOLE plasma
Homo sapiens
2%
300 mg 1 times / day multiple, intravenous
POSACONAZOLE plasma
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Drug as perpetrator​

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
Injection: Loading dose: 300 mg Noxafil injection intravenously twice a day on the first day. Maintenance dose: 300 mg Noxafil injection intravenously once a day, starting on the second day. Oral suspension: Prophylaxis of invasive Aspergillus and Candida infections: 200 mg (5 mL) three times a day. Oropharyngeal Candidiasis: Loading dose: 100 mg (2.5 mL) twice a day on the first day. Maintenance dose: 100 mg (2.5 mL) once a day for 13 days.
Route of Administration: Other
In Vitro Use Guide
Unknown