Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C52H74Cl2O18 |
Molecular Weight | 1058.039 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 14 / 14 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]4(O[C@@H]1[C@@H](CC)\C=C(C)\[C@@H](O)C\C=C\C=C(CO[C@@H]2O[C@H](C)[C@@H](OC(=O)C3=C(CC)C(Cl)=C(O)C(Cl)=C3O)[C@H](O)[C@@H]2OC)\C(=O)O[C@@H](C\C=C(C)\C=C1/C)[C@@H](C)O)OC(C)(C)[C@@H](OC(=O)C(C)C)[C@H](O)[C@@H]4O
InChI
InChIKey=ZVGNESXIJDCBKN-UUEYKCAUSA-N
InChI=1S/C52H74Cl2O18/c1-13-30-22-26(6)33(56)18-16-15-17-31(23-66-51-45(65-12)42(61)44(29(9)67-51)69-49(64)35-32(14-2)36(53)39(58)37(54)38(35)57)48(63)68-34(28(8)55)20-19-25(5)21-27(7)43(30)70-50-41(60)40(59)46(52(10,11)72-50)71-47(62)24(3)4/h15-17,19,21-22,24,28-30,33-34,40-46,50-51,55-61H,13-14,18,20,23H2,1-12H3/b16-15+,25-19+,26-22+,27-21+,31-17+/t28-,29-,30+,33+,34+,40-,41+,42+,43+,44-,45+,46+,50-,51-/m1/s1
Molecular Formula | C52H74Cl2O18 |
Molecular Weight | 1058.039 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 14 / 14 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/807545; https://www.ncbi.nlm.nih.gov/pubmed/?term=20509714; http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002087/human_med_001511.jsp&mid=WC0b01ac058001d124
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/807545; https://www.ncbi.nlm.nih.gov/pubmed/?term=20509714; http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002087/human_med_001511.jsp&mid=WC0b01ac058001d124
Fidaxomicin (trade names Dificid, Dificlir in Europe) is the first in a new class of narrow spectrum macrocyclic antibiotic drugs indicated for treatment of Clostridium difficile-associated diarrhea. Lipiarmycin (fidaxomicin), a metabolite of Actinoplanes deccanensis nov. sp. was first isolated in pure form in 1970s and was considered as antibiotic from its chemical and physico-chemical characteristics. It demonstrated high activity against Gram-positive bacteria, including strains resistant to the medically important antibiotics and protected mice experimentally infected with Streptococcus haemolyticus. Fidaxomicin is non-systemic, meaning it is minimally absorbed into the bloodstream, it is bactericidal, and it has demonstrated selective eradication of pathogenic Clostridium difficile with minimal disruption to the multiple species of bacteria that make up the normal, healthy intestinal flora. Although the exact mechanism of action has yet to be fully elucidated, fidaxomicin may bind to and inhibit bacterial DNA-dependent RNA polymerase, thereby inhibiting the initiation of bacterial RNA synthesis. When orally administered, this agent is minimally absorbed into the systemic circulation, acting locally in the gastrointestinal tract. Fidaxomicin appears to be active against pathogenic Gram-positive bacteria, such as clostridia, enterococci, and staphylococci, but does not appear to be active against other beneficial intestinal bacteria. The maintenance of normal physiological conditions in the colon can reduce the probability of Clostridium difficile infection recurrence. It is marketed by Cubist Pharmaceuticals after acquisition of its originating company Optimer Pharmaceuticals.
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/807545
Curator's Comment: Lipiarmycin, a metabolite of Actinoplanes deccanensis nov. sp. has been isolated in pure form in 1970s and has been considered a new antibiotic. The compound was later being jointly developed by Optimer and Par Pharmaceuticals for the treatment of Clostridium difficile infections [https://www.ncbi.nlm.nih.gov/pubmed/?term=20509714]
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2363852 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | DIFICID Approved UseIndicated in adults (≥18 years of age) for treatment of Clostridium difficile-associated diarrhea (CDAD). Launch Date2011 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5.2 ng/mL |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
FIDAXOMICIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
62.9 ng × h/mL |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
FIDAXOMICIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
11.7 h |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
FIDAXOMICIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
200 mg 2 times / day multiple, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: Page: p.4 |
unhealthy n = 564 Health Status: unhealthy Condition: C. difficile-associated diarrhea Population Size: 564 Sources: Page: p.4 |
Disc. AE: Vomiting... AEs leading to discontinuation/dose reduction: Vomiting (0.5%) Sources: Page: p.4 |
200 mg 2 times / day multiple, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: C. difficile-associated diarrhea Sources: Page: p.1 |
Disc. AE: Hypersensitivity reaction, Multidrug resistant bacterial infection... AEs leading to discontinuation/dose reduction: Hypersensitivity reaction Sources: Page: p.1Multidrug resistant bacterial infection |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Vomiting | 0.5% Disc. AE |
200 mg 2 times / day multiple, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: Page: p.4 |
unhealthy n = 564 Health Status: unhealthy Condition: C. difficile-associated diarrhea Population Size: 564 Sources: Page: p.4 |
Hypersensitivity reaction | Disc. AE | 200 mg 2 times / day multiple, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: C. difficile-associated diarrhea Sources: Page: p.1 |
Multidrug resistant bacterial infection | Disc. AE | 200 mg 2 times / day multiple, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: C. difficile-associated diarrhea Sources: Page: p.1 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.pmda.go.jp/drugs/2018/P20180626001/800126000_23000AMX00480000_A100_1.pdf#page=18 Page: (PMDA in Japanese) 18-19 |
no | |||
Sources: https://www.pmda.go.jp/drugs/2018/P20180626001/800126000_23000AMX00480000_A100_1.pdf#page=18 Page: (PMDA in Japanese) 18-19 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=52 Page: 11, 26, 33, 52-53 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=52 Page: 11, 26, 33, 52-53 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=52 Page: 11, 26, 33, 52-53 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=52 Page: 11, 26, 33, 52-53 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=52 Page: 11, 26, 33, 52-53 |
no | |||
Sources: https://www.pmda.go.jp/drugs/2018/P20180626001/800126000_23000AMX00480000_A100_1.pdf#page=18 Page: (PMDA in Japanese) 18-19 |
no | |||
Sources: https://www.pmda.go.jp/drugs/2018/P20180626001/800126000_23000AMX00480000_A100_1.pdf#page=19 Page: (PMDA in Japanese) 18-19 |
no | |||
Sources: https://www.pmda.go.jp/drugs/2018/P20180626001/800126000_23000AMX00480000_A100_1.pdf#page=19 Page: (PMDA in Japanese) 18-19 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=34 Page: 12, 33, 34-37, 58-60, 84-92 |
yes | likely (co-administration study) Comment: Caco-2 cells, efflux ratio = 73.9, Effluxes were decreased by >50% in the presence of test P-gp inhibitors, cyclosporine and ketoconazole; Coadministration of cyclosporine (200 mg x 1, P-gp inhibitor) increased Fidaxomicin (200 mg x 1) Cmax by 315% and AUCinf by 92%., Efficacy rates of fidaxomicin surpassed those of PO vancomycin for nearly all endpoints and analysis populations, regardless of P-gp inhibitor use. Fidaxomicin may be co-administered with P-gp inhibitors. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=34 Page: 12, 33, 34-37, 58-60, 84-92 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=34 Page: 12, 33, 34-37, 58-60, 84-92 |
yes | likely (co-administration study) Comment: Caco-2 cells, efflux ratio = 15.7; Coadministration of cyclosporine (P-gp inhibitor) increased Fidaxomicin Cmax by 851% and AUCinf by 311%. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=34 Page: 12, 33, 34-37, 58-60, 84-92 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000PharmR.pdf#page=30 Page: (Pharm) 30 |
Sample Use Guides
One 200 mg tablet orally twice daily for 10 days with or without food
Route of Administration:
Oral
Substance Class |
Chemical
Created
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admin
on
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Record UNII |
Z5N076G8YQ
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Record Status |
Validated (UNII)
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A07AA12
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FDA ORPHAN DRUG |
325210
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N0000175431
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NCI_THESAURUS |
C261
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QA07AA12
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LIVERTOX |
NBK548928
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m5378
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Fidaxomicin
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FIDAXOMICIN
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CHEMBL1255800
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C66979
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Related Record | Type | Details | ||
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TRANSPORTER -> SUBSTRATE | |||
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EXCRETED UNCHANGED |
FECAL
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METABOLIC ENZYME -> INHIBITOR |
IC50
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TRANSPORTER -> INHIBITOR |
IC50
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METABOLIC ENZYME -> INHIBITOR |
Fidaxomicin and OP-1118 exhibited inhibitory potential for prominent intestinal CYP isoenzymes (CYP3A4, CYP2C9, and CYP2C19) in in vitro studies with human liver microsomes, based on estimated intestinal concentrations (fidaxomicin [I]2, 800 μg/mL).
IC50
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METABOLIC ENZYME -> INHIBITOR |
Fidaxomicin and OP-1118 exhibited inhibitory potential for prominent intestinal CYP isoenzymes (CYP3A4, CYP2C9, and CYP2C19) in in vitro studies with human liver microsomes, based on estimated intestinal concentrations (fidaxomicin [I]2, 800 μg/mL).
IC50
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EXCRETED UNCHANGED |
FECAL
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TARGET ORGANISM->INHIBITOR |
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METABOLITE ACTIVE -> PARENT | |||
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METABOLITE LESS ACTIVE -> PARENT |
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Tmax | PHARMACOKINETIC |
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SINGLE DOSE |
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Biological Half-life | PHARMACOKINETIC |
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