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Purity: ≥98%
Fidaxomicin (formerlyOPT-80, PAR-101; PAR101; OPT80; Dificid; Dificlir; Clostomicin B1; Difimicin; Lipiarmycin; Tiacumicin B) is a narrow spectrum macrocyclic antibiotic agent and a naturally occuring fermentation product extracted from the actinomycete Dactylosporangium aurantiacum subspecies hamdenesisthat. As an RNA polymerase inhibitor, fidaxomicin binds to the DNA template–RNA polymerase (RNAP) complex before the open RNAP–DNA complex forms, which is when transcription starts.
| Targets |
RNA polymerase
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| ln Vitro |
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| ln Vivo |
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| Animal Protocol |
Male Golden Syrian hamsters (80-100 g, Hamster model for pseudomembranous colitis)
0.2, 1, and 5 mg/kg Orally, once a day for 5 days, beginning 8 h after infection |
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Following oral administration of a single dose of 200 mg fidaxomicin in healthy adults, the Cmax of fidaxomicin and its main metabolite OP-1118 were 5.20 ± 2.81 ng/mL and 12.0 ± 6.06, respectively. The median Tmax of fidaxomicin was 2 hours. The systemic absorption of fidaxomicin following oral administration is minimal. In a food-effect study involving healthy adults in either with a high-fat meal versus under fasting conditions, the Cmax of fidaxomicin and OP-1118 were decreased by 21.5% and 33.4%, respectively; however, this effect is deemed to be clinically insignificant as the therapeutic action of fidaxomicin does not depend on drug concentrations in the systemic circulation. Following oral administration, fidaxomicin is mainly excreted in feces. More than 92% of the dose was recovered in the faces as either the unchanged parent drug or metabolites in one study consisting of healthy adults receiving single doses of 200 mg and 300 mg of fidaxomicin. In another study of healthy adults, approximately 0.59% fo the oral dose (200 mg) administered was recovered in the urine as the main metabolite, OP-1118. Fidaxomicin is mainly confined to the gastrointestinal tract when orally administered. There is limited information on the volume of distribution of fidaxomicin. There is limited information on the clearance of fidaxomicin. Metabolism / Metabolites Following oral administration, fidaxomicin is transformed to its main and pharmacologically active metabolite, OP-1118, via hydrolysis at the isobutyryl ester. As cytochrome enzymes are not involved in the metabolism of fidaxomicin, it is speculated that this biotransformation is mediated by gastric acid or enzymatic activity of intestinal microsomes. Biological Half-Life Following oral administration of a single dose of 200 mg fidaxomicin in healthy adults, the elimination half-life of fidaxomicin was approximately 11.7 ± 4.80 hours. |
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| Toxicity/Toxicokinetics |
Hepatotoxicity
In large clinical trials, therapy with fidaxomicin for ten days was associated with a low rate of serum aminotransferase elevations [1% to 3.2%], but rates with comparator agents such as vancomycin were similar [up to 2.7%]. There have been no reports of clinically apparent liver injury attributed to fidaxomicin. However, other oral macrolide antibiotics have been linked to many episodes of acute liver injury which can be severe and have resulted in fatalities. The onset of macrolide associated liver injury is typically 1 to 3 weeks after starting the drug and can arise after it is stopped. The injury is typically cholestatic, but can be mixed or hepatocellular. The hepatocellular cases are more likely to be severe and can result in acute liver failure. However, in most instances, recovery occurs within 4 to 8 weeks of withdrawal of the macrolide. No such cases, however, have been linked to use of fidaxomicin, which unlike the other macrolides is not absorbed orally. Likelihood score: E (unlikely cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the use of fidaxomicin during breastfeeding. Because it is poorly absorbed orally, it is not likely to reach the bloodstream of the infant or cause any adverse effects in breastfed infants. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Since fidaxomicin has minimal systemic absorption following oral administration, there is limited information on the plasma protein binding profile of fidoxamicin. |
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| References | ||
| Additional Infomation |
Pharmacodynamics
Fidaxomicin has a narrow-spectrum antibacterial profile, with potent bactericidal activity specifically against C. difficile. The minimum inhibitory concentration for 90% of organisms for fidaxomicin against _C. difficile_ ranged from 0.0078 to 2 μg/mL _in vitro_. The bactericidal activity of fidaxomicin is time-dependent. Other than _C. difficile_, fidaxomicin has moderate inhibitory activity against Gram-positive bacteria (_S. aureus_ and _Enterococcus spp._) and poor activity against normal colonic flora, including anaerobes and enteric Gram-negative bacilli. Isolates of _C. difficile_ that are resistant to rifamycins or other antimicrobial classes (such as cephalosporins, fluoroquinolones, clindamycin) were not shown to be cross-resistant to fidaxomicin. |
| Molecular Formula |
C52H74CL2O18
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| Molecular Weight |
1058.04
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| Exact Mass |
1056.425
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| Elemental Analysis |
C, 54.28; H, 5.04; F, 4.52; N, 13.33; O, 22.83
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| CAS # |
873857-62-6
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| Related CAS # |
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| PubChem CID |
10034073
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
1046.4±65.0 °C at 760 mmHg
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| Flash Point |
586.7±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.590
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| LogP |
10.73
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| Hydrogen Bond Donor Count |
7
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| Hydrogen Bond Acceptor Count |
18
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
72
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| Complexity |
1970
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| Defined Atom Stereocenter Count |
14
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| SMILES |
ClC1=C(C(=C(C(=C1C([H])([H])C([H])([H])[H])C(=O)O[C@]1([H])[C@@]([H])(C([H])([H])[H])O[C@]([H])([C@]([H])([C@@]1([H])O[H])OC([H])([H])[H])OC([H])([H])C1C(=O)O[C@]([H])([C@@]([H])(C([H])([H])[H])O[H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])=C(C([H])([H])[H])[C@@]([H])([C@]([H])(C([H])=C(C([H])([H])[H])[C@]([H])(C([H])([H])C([H])=C([H])C=1[H])O[H])C([H])([H])C([H])([H])[H])O[C@@]1([H])[C@]([H])([C@]([H])([C@@]([H])(C(C([H])([H])[H])(C([H])([H])[H])O1)OC(C([H])(C([H])([H])[H])C([H])([H])[H])=O)O[H])O[H])O[H])Cl)O[H] |c:63,70,81,93,96|
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| InChi Key |
ZVGNESXIJDCBKN-UUEYKCAUSA-N
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| InChi Code |
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
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| Chemical Name |
[(2R,3S,4S,5S,6R)-6-[[(3E,5E,8S,9E,11S,12R,13E,15E,18S)-12-[(2R,3S,4R,5S)-3,4-dihydroxy-6,6-dimethyl-5-(2-methylpropanoyloxy)oxan-2-yl]oxy-11-ethyl-8-hydroxy-18-[(1R)-1-hydroxyethyl]-9,13,15-trimethyl-2-oxo-1-oxacyclooctadeca-3,5,9,13,15-pentaen-3-yl]methoxy]-4-hydroxy-5-methoxy-2-methyloxan-3-yl] 3,5-dichloro-2-ethyl-4,6-dihydroxybenzoate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.36 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.36 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9451 mL | 4.7257 mL | 9.4514 mL | |
| 5 mM | 0.1890 mL | 0.9451 mL | 1.8903 mL | |
| 10 mM | 0.0945 mL | 0.4726 mL | 0.9451 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05201079 | Recruiting | Biological: MBK-01 Drug: Dificlir |
Recurrent Clostridium Difficile Infection Primary Clostridium Difficile Infection |
Mikrobiomik Healthcare Company S.L. |
October 29, 2021 | Phase 3 |
| NCT05266807 | Recruiting | Drug: oral capsulized Fecal Microbiota Transplantation Drug: Vancomycin or Fidaxomicin |
Clostridioides Difficile Infection |
Benoit Guery | August 16, 2022 | Phase 3 |
| NCT02667418 | Recruiting | Drug: Fidaxomicin Drug: Vancomycin |
Fidaxomicin Difficile |
VA Office of Research and Development |
December 21, 2015 | Phase 4 |
| NCT02083627 | Completed | Drug: fidaxomicin BDrug: rosuvastatin |
Intestinal Absorption Healthy Subjects |
Astellas Pharma Europe B.V. | February 2013 | Phase 1 |
| NCT01818141 | Active Recruiting |
Drug: Vancomycin Drug: Fidaxomicin |
Clostridium Difficile Infection | Hartford Hospital | October 17, 2012 | Phase 4 |
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