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Oritavancin (formerly known as LY333328; LY-333328; Orbactiv) is a novel semisynthetic glycopeptide antibiotic medication approved for the treatment of serious Gram-positive bacterial infections. It is a lipoglycopeptide analog of vancomycin containing the heptapeptide core common to all glycopeptides. On August 6, 2014, the FDA approved oritavancin for treatment of skin infections. Oritavancin possesses potent and rapid bactericidal activity in vitro against a broad spectrum of both resistant and susceptible Gram-positive bacteria, including Staphylococcus aureus, MRSA, enterococci, and streptococci. Oritavancin was more active than either metronidazole or vancomycin against strains of Clostridium difficile tested. Oritavancin has potential use as a therapy for exposure to Bacillus anthracis, the Gram-positive bacterium that causes anthrax, having demonstrated efficacy in a mouse model both before and after exposure to the bacterium.
| Targets |
Glycopeptide; macrolides antibiotic/bactericidal; cell wall synthesis
Oritavancin (LY333328) targets bacterial cell wall synthesis by binding to the D-alanyl-D-alanine (D-Ala-D-Ala) terminus of peptidoglycan precursors, with minimum inhibitory concentrations (MIC) against susceptible bacteria ranging from 0.015 μg/mL to 2 μg/mL [2] |
|---|---|
| ln Vitro |
Oritavancin, a semisynthetic lipoglycopeptide with activity against gram-positive bacteria, has multiple mechanisms of action, including the inhibition of cell wall synthesis and the perturbation of the membrane potential. [1]
Both oritavancin and vancomycin achieved 99.9% (3-log) kill, with oritavancin achieving the limit of detection (10(2) CFU/ml) within 1 h and vancomycin achieving this limit at 24 h for both isolates. Detection of resistance was not observed for oritavancin or vancomycin during the 48-h experiments. The key pharmacodynamic parameter for oritavancin has not been well defined. In our experiment, the ratios of the area under the curve from 0 to 24 h to the MIC of oritavancin, oritavancin plus albumin, and vancomycin for both isolates were greater than 944.5, and the ratios of the maximum concentration of drug in serum to the MIC ranged from 73.7 to 7188.5. T>MIC was 100% for oritavancin and vancomycin for both isolates. Oritavancin is a unique and potent antimicrobial that warrants further investigation against multidrug-resistant S. pneumoniae[2]. Against multidrug-resistant Streptococcus pneumoniae (including penicillin-resistant and erythromycin-resistant strains), Oritavancin (LY333328) exhibited potent antibacterial activity with MIC90 values of 0.125 μg/mL, which was 4-8 fold more potent than vancomycin (MIC90 = 0.5-1 μg/mL) [2] - In an in vitro pharmacodynamic model simulating human serum pharmacokinetics, Oritavancin (LY333328) at concentrations corresponding to 2 mg/kg intravenous dose achieved >99% reduction in viable counts of multidrug-resistant S. pneumoniae within 24 hours, with sustained bactericidal effect for up to 72 hours [2] - Polysorbate 80 (0.01-0.1%) significantly reduced the binding of Oritavancin (LY333328) to plastic surfaces in susceptibility testing, resulting in 2-4 fold lower MIC values compared to tests without polysorbate 80 (e.g., MIC for Staphylococcus aureus decreased from 0.5 μg/mL to 0.125 μg/mL) [1] - Oritavancin (LY333328) showed bactericidal activity against Bacillus anthracis (parent strain and capsule-deficient mutant) with MIC values of 0.06 μg/mL and 0.03 μg/mL, respectively [3] - For acute bacterial skin and skin structure infection (ABSSSI)-related pathogens (S. aureus, Streptococcus pyogenes, Enterococcus faecalis), Oritavancin (LY333328) exhibited MIC90 values of 0.125 μg/mL, 0.03 μg/mL, and 0.25 μg/mL, respectively, with bactericidal activity (minimum bactericidal concentration [MBC]/MIC ratio ≤ 4) [4] |
| ln Vivo |
In postexposure prophylaxis dose-ranging studies, a single intravenous (i.v.) dose of oritavancin of 5, 15, or 50 mg/kg 24 h after a challenge with 50 to 75 times the median lethal dose of Ames strain spores provided 40, 70, and 100% proportional survival, respectively, at 30 days postchallenge. Untreated animals died within 4 days of challenge, whereas 90% of control animals receiving ciprofloxacin at 30 mg/kg intraperitoneally twice daily for 14 days starting 24 h after challenge survived. Oritavancin demonstrated significant activity post symptom development; a single i.v. dose of 50 mg/kg administered 42 h after challenge provided 56% proportional survival at 30 days. In a preexposure prophylaxis study, a single i.v. oritavancin dose of 50 mg/kg administered 1, 7, 14, or 28 days before lethal challenge protected 90, 100, 100, and 20% of mice at 30 days; mice treated with ciprofloxacin 24 h or 24 and 12 h before challenge all died within 5 days. Efficacy in pre- and postexposure models of inhalation anthrax, together with a demonstrated low propensity to engender resistance, promotes further study of oritavancin pharmacokinetics and efficacy in nonhuman primate models[3].
In a murine model of Bacillus anthracis spore inhalation anthrax, a single intravenous dose of Oritavancin (LY333328) at 10 mg/kg, 25 mg/kg, or 50 mg/kg administered 24 hours post-infection resulted in survival rates of 60%, 90%, and 100%, respectively; vancomycin (50 mg/kg, twice daily for 5 days) achieved 80% survival [3] - Oritavancin (LY333328) (25 mg/kg, IV) significantly reduced bacterial loads in the lungs, spleen, and blood of infected mice by >3 log10 CFU/organ compared to untreated controls at 48 hours post-infection [3] - In clinical studies for ABSSSI, a single intravenous dose of Oritavancin (LY333328) (1200 mg) achieved clinical cure rates of 86-92% at test of cure (7-14 days post-treatment), non-inferior to vancomycin (1 g IV twice daily for 7-10 days) [4] - The compound resolved signs of infection (erythema, edema, pain) in ABSSSI patients within 3-7 days, with sustained clinical response up to 28 days post-treatment [4] |
| Enzyme Assay |
Susceptibility of B. anthracis strains to oritavancin as measured by broth microdilution. [3]
Oritavancin MICs were determined by broth microdilution in 96-well plates according to guidelines of the Clinical and Laboratory Standards Institute. As recommended in guideline M100-S18, polysorbate 80 was included at a final concentration of 0.002% throughout drug dissolution and all steps of the assay to minimize oritavancin binding to surfaces. To determine the impact, if any, of polysorbate 80 upon oritavancin MICs for B. anthracis, a parallel broth microdilution assay was conducted in which oritavancin was dissolved in water and drug dilutions were prepared without polysorbate 80. Quality control of oritavancin dilutions was established by using S. aureus ATCC 29213 with polysorbate 80 at 0.002% throughout; an acceptable range of oritavancin MICs against this strain is 0.015 to 0.12 μg/ml. Titration of polysorbate 80 in oritavancin MIC test. [1] To determine the polysorbate 80 concentration dependence of the oritavancin MICs, broth microdilution susceptibility tests with S. aureus ATCC 29213 as an indicator strain were performed according to the CLSI M7-A7 methodology, except that various test concentrations of polysorbate 80 were included at the drug dissolution step and were maintained at the test concentration onwards.[1] Order of addition of polysorbate 80 in oritavancin MIC test. [1] To determine whether the order of addition of polysorbate 80 affected the oritavancin MICs, broth microdilution susceptibility tests were performed with S. aureus ATCC 29213 as an indicator strain, in which oritavancin was either dissolved in 0.002% polysorbate 80 and diluted and assayed by maintaining polysorbate 80 at 0.002% or dissolved and diluted in water and then assayed by adding inoculum with or without polysorbate 80. When polysorbate 80 was present, it was added at a final concentration of 0.002%, as described in the CLSI guidelines for dalbavancin. Bacterial peptidoglycan binding assay: Purified bacterial cell wall peptidoglycan fragments containing D-Ala-D-Ala termini were immobilized on a solid phase. Serial dilutions of Oritavancin (LY333328) were incubated with the immobilized peptidoglycan, and unbound compound was washed away. Bound Oritavancin (LY333328) was detected using a specific antibody, and binding affinity was quantified by absorbance measurement [2] |
| Cell Assay |
In vitro pharmacodynamic model. [2]
The in vitro pharmacodynamic model consists of a 250-ml one-compartment glass chamber with ports for the addition and removal of the THB with 0.5% yeast extract with or without albumin, injection of antibiotics, and removal of samples. Prior to each experiment, colonies from an overnight growth of bacteria on TSA plates with 5% SB were added to THB with 0.5% yeast extract to obtain a concentration of 106 CFU/ml. Fresh stock solutions of oritavancin and vancomycin were prepared daily and were stored at 2 to 8°C between dose administration times. Experimental regimens simulated antibiotic concentrations achieved in human plasma. Vancomycin was administered at a dose of 1 g every 12 h (four doses given) to achieve a peak concentration in serum (Cmax) of 30 μg/ml and a trough concentration of 7.5 μg/ml. To achieve targeted concentrations of oritavancin in plasma during the first 48 h of dosing in humans, oritavancin was administered at a loading dose of 5 mg/kg of body weight at 0 h, followed by 4 mg/kg at 24 h, to achieve a peak concentration of 100 μg/ml and 24-h trough concentration of 15 μg/ml. Each antibiotic was administered as a bolus into the models over 30 s using a hypodermic syringe. Fresh medium (SMHB) was continuously supplied and removed from the model along with the drug via a peristaltic pump set to simulate the half-lives (t1/2s) of vancomycin (6.5 h) and oritavancin (t1/2 at α phase [t1/2α] = 2 h); the pump ran in this manner for 8 h after dosing and then was changed to simulate a t1/2 of 12.3 h for the remaining 16 h of the 24 h dosing period. Each model apparatus was placed in a water bath and maintained at 37°C for the entire 48 h study period. The pharmacodynamic model experiments were performed in duplicate, simultaneously, in order to ensure reproducibility.
Minimum inhibitory concentration (MIC) assay: Bacterial strains (S. pneumoniae, S. aureus, B. anthracis, etc.) were inoculated into cation-adjusted Mueller-Hinton broth (CAMHB) containing serial dilutions of Oritavancin (LY333328) (with or without 0.05% polysorbate 80). Plates were incubated at 35°C for 18-24 hours, and MIC was defined as the lowest concentration inhibiting visible bacterial growth [1] - In vitro pharmacodynamic model: A two-compartment model was used to simulate human serum concentrations of Oritavancin (LY333328) (2 mg/kg IV dose). Bacteria were inoculated into the model, and viable counts were determined at 0, 2, 4, 8, 24, 48, and 72 hours by plating on agar plates and counting colonies [2] - Bactericidal activity assay: MBC was determined by subculturing 100 μL of broth from MIC assay wells with no visible growth onto agar plates. MBC was defined as the lowest concentration resulting in ≥99.9% reduction in viable bacterial counts compared to the initial inoculum [4] |
| Animal Protocol |
Murine B. anthracis spore inhalation model: Female BALB/c mice (6-8 weeks old) were exposed to aerosolized B. anthracis spores (100×LD50) in an inhalation chamber. Oritavancin (LY333328) was dissolved in normal saline and administered as a single intravenous injection at 10 mg/kg, 25 mg/kg, or 50 mg/kg 24 hours post-infection. Control groups received normal saline or vancomycin (50 mg/kg IV twice daily for 5 days). Mice were monitored for survival for 14 days, and bacterial loads in organs were quantified at 48 hours post-infection [3]
- ABSSSI clinical study protocol: Adult patients with ABSSSI (erythema/edema ≥75 cm2, plus purulence or positive culture) were randomized to receive a single IV dose of Oritavancin (LY333328) (1200 mg) or vancomycin (1 g IV twice daily) for 7-10 days. Clinical cure was defined as complete resolution or significant improvement of infection signs/symptoms at 7-14 days post-treatment [4] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Pharmacokinetic analysis of orivacin showed a Cmax of 138 μg/mL and an AUC0-∞ of 2800 μg•h/mL. In one healthy volunteer, after an 800 mg dose, the AUC0-t was 1111 μg•h/mL. Another pharmacokinetic study reported a Cmax of 4.7–7.6 μg/mL, typically reached within 24 hours of administration. Orivacin is excreted unchanged in urine and feces. Less than 5% of the drug is recovered in urine, and 1% in feces. The estimated volume of distribution of orivacin is 87.6 L, indicating its extensive tissue distribution. The clearance of orivacin is approximately 0.445 L/h. One study showed a renal clearance of 0.457 mL/min. Metabolism/Metabolites In vitro studies of human hepatocytes have shown that orivancin is not metabolized and is excreted unchanged. Biological Half-Life The average terminal half-life of orivancin is approximately 245 hours. Pharmacokinetic studies have shown that the terminal half-life of orivancin (LY333328) is 135.8-273.8 hours. In humans, after a single intravenous injection of 1200 mg orivancin (LY333328), the peak plasma concentration (Cmax) was 113.8 μg/mL, the area under the plasma concentration-time curve (AUC0-∞) was 3582 μg·h/mL, and the terminal half-life (t1/2) was 393 hours[4]. The compound has a large apparent volume of distribution (Vdss = 10.2 L/kg), indicating its extensive tissue penetration and high concentrations in the skin and soft tissues (target sites of ABSSSI) [4]. Orivancin (LY333328) is mainly cleared via non-renal routes (renal excretion accounts for <10% of total clearance) [4]. - Orivancin (LY333328) has a plasma protein binding rate of 85-90% in human plasma [4]. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Summary of Use During Lactation Because orivacin is poorly absorbed orally, it is unlikely to enter the infant's bloodstream and is unlikely to cause any adverse reactions in breastfed infants. Infants should be monitored for gastrointestinal reactions such as diarrhea, vomiting, and candidiasis (e.g., thrush, diaper rash). However, since there is currently no published experience regarding the use of orivacin during lactation, alternative medications may be preferred, especially in breastfed newborns or premature infants. ◉ Effects on Breastfed Infants As of the revision date, no relevant published information was found. ◉ Effects on Lactation and Breast Milk As of the revision date, no relevant published information was found. Protein Binding Orivacin binds to plasma proteins at a rate of approximately 85%. In the ABSSSI clinical trials, Olivin (LY333328) (1200 mg single intravenous dose) had a good safety profile, with the most common adverse events being headache (12%), nausea (8%), and infusion-related reactions (6%) [4] - In mouse toxicity studies, doses up to 50 mg/kg (single intravenous dose) did not cause significant weight loss, mortality, or histopathological abnormalities in major organs (liver, kidney, heart, lungs) [3] - The compound does not inhibit cytochrome P450 isoenzymes, and no significant drug interactions were observed in clinical studies [4] |
| References |
[1]. Effect of polysorbate 80 on oritavancin binding to plastic surfaces: implications for susceptibility testing. Antimicrob Agents Chemother. 2008 May;52(5):1597-1603.
[2]. Activity of oritavancin (LY333328), an investigational glycopeptide, compared to that of vancomycin against multidrug-resistant Streptococcus pneumoniae in an in vitro pharmacodynamic model. Antimicrob Agents Chemother. 2001 Mar;45(3):706-9.
[3]. Efficacy of oritavancin in a murine model of Bacillus anthracis spore inhalation anthrax. Antimicrob Agents Chemother. 2008 Sep;52(9):3350-7.
[4]. Oritavancin for the treatment of acute bacterial skin and skin structure infections: an evidence-based review. Core Evid. 2015 Feb 11;10:39-47. |
| Additional Infomation |
Oritavancin is a semi-synthetic glycopeptide antibiotic (in its dihydrogen phosphate form) used to treat acute bacterial skin and soft tissue infections caused or suspected of being caused by susceptible strains of certain Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus [MRSA]. It has both antimicrobial and antimicrobial action. Orivacin is a disaccharide derivative, a glycopeptide antibiotic, and a semi-synthetic derivative whose function is related to vancomycin aglycone. Orivacin is a glycopeptide antibiotic developed by the pharmaceutical company (acquired by Novartis) for the treatment of skin infections. Orivacin was first approved by the U.S. Food and Drug Administration (FDA) in 2014, with a formulation designed to combat susceptible Gram-positive bacteria that cause skin and soft tissue infections. Orivacin can be administered as a single dose and has been shown to be non-inferior to a full course of vancomycin. On March 12, 2021, the FDA approved Kimyrsa, a drug that requires only a single 1-hour intravenous infusion to complete a course of treatment. Another FDA-approved oribancin product, Orbactiv, requires a lower dose of 400 mg administered via intravenous infusion over 3 hours. Kimyrsa, marketed by Melinta Therapeutics, is effective and provides rapid treatment for skin and soft tissue infections. Oribancin is a lipopeptide antibacterial agent. Its mechanism of action is as an inhibitor of cytochrome P450 2C19, cytochrome P450 2C9, cytochrome P450 3A4, and cytochrome P450 2D6. See also: Oribancin diphosphate (active ingredient). Indications Oribancin is indicated for the treatment of acute bacterial skin and soft tissue infections (including subcutaneous tissue) in adults. It is used for confirmed/suspected infections caused by specified Gram-positive bacteria sensitive to oribancin. Oribancin is available in two formulations: a 400 mg dose administered over 3 hours and a 1200 mg dose administered over 1 hour. Both formulations are indicated for the treatment of skin and soft tissue infections caused by Gram-positive bacteria susceptible to orivacin in adults. Due to regional variations in antimicrobial susceptibility patterns, local susceptibility testing results should be consulted before use to ensure adequate antimicrobial coverage against the relevant pathogens.
FDA Label Tenkasi is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) in adults and children 3 months and older (see Sections 4.2, 4.4, and 5.1). Official guidelines on the rational use of antimicrobial agents should be consulted. Mechanism of Action The cell wall is essential for bacterial survival and replication and is therefore a primary target for antibiotic therapy. Orivacin combats susceptible Gram-positive bacteria through three distinct mechanisms. First, it binds to the peptide chain of peptidoglycan precursors, inhibiting transglycosylation (polymerization). This process typically occurs during cell wall synthesis. Second, orivacin inhibits cross-linking during bacterial cell wall biosynthesis by binding to a pentaglycine peptide bridging fragment in the cell wall. Finally, the drug can also exert its effects by disrupting the bacterial cell membrane, interfering with its integrity, and ultimately causing cell death through a variety of mechanisms. Olivansin (LY333328) is a semi-synthetic glycopeptide antibiotic with a dual mechanism of action: it binds to the D-Ala-D-Ala terminus to inhibit cell wall synthesis and disrupt the integrity of the bacterial cell membrane [2] - It is effective against Gram-positive bacteria, including multidrug-resistant strains (methicillin-resistant Staphylococcus aureus [MRSA], vancomycin-intermediate Staphylococcus aureus [VISA], penicillin-resistant Streptococcus pneumoniae) [2] - Its long half-life (about 16 days) allows ABSSSI to be administered as a single dose without the need for multiple daily doses or prolonged intravenous infusions [4] - It is recommended to use polysorbate 80 in the drug sensitivity test to prevent Olivansin (LY333328) from binding to plastic surfaces, which may lead to a false increase in MIC values [1] |
| Molecular Formula |
C86H97N10O26CL3
|
|---|---|
| Molecular Weight |
1793.10078
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| Exact Mass |
1790.56
|
| Elemental Analysis |
C, 57.61; H, 5.45; Cl, 5.93; N, 7.81; O, 23.20
|
| CAS # |
171099-57-3
|
| Related CAS # |
Oritavancin diphosphate;192564-14-0
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| PubChem CID |
16136912
|
| Appearance |
Solid powder
|
| LogP |
8.57
|
| Hydrogen Bond Donor Count |
20
|
| Hydrogen Bond Acceptor Count |
29
|
| Rotatable Bond Count |
19
|
| Heavy Atom Count |
125
|
| Complexity |
3700
|
| Defined Atom Stereocenter Count |
22
|
| SMILES |
CC(C[C@H](C(N[C@H]1C(=O)N[C@@H](CC(=O)N)C(=O)N[C@H]2C(N[C@H]3C(=O)N[C@@H]([C@@H](C4C=CC(OC5C=C2C=C(C=5O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O[C@@H]2O[C@@H](C)[C@H](O)[C@@](C)(NCC5C=CC(C6C=CC(Cl)=CC=6)=CC=5)C2)OC2C=CC(=CC=2Cl)[C@H]1O)=C(Cl)C=4)O[C@@H]1O[C@@H](C)[C@H](O)[C@@](C)(N)C1)C(=O)N[C@H](C(=O)O)C1=CC(=CC(O)=C1C1=C(C=CC3=C1)O)O)=O)=O)NC)C
|
| InChi Key |
PWTROOMOPLCZHB-BHYQHFGMSA-N
|
| InChi Code |
InChI=1S/C86H97Cl3N10O26.2H3O4P/c1-35(2)22-51(92-7)77(110)98-67-69(105)42-15-20-55(49(88)24-42)120-57-26-44-27-58(73(57)125-84-74(71(107)70(106)59(34-100)122-84)124-62-32-86(6,76(109)37(4)119-62)93-33-38-8-10-39(11-9-38)40-12-17-45(87)18-13-40)121-56-21-16-43(25-50(56)89)72(123-61-31-85(5,91)75(108)36(3)118-61)68-82(115)97-66(83(116)117)48-28-46(101)29-54(103)63(48)47-23-41(14-19-53(47)102)64(79(112)99-68)96-80(113)65(44)95-78(111)52(30-60(90)104)94-81(67)1142*1-5(2,3)4/h8-21,23-29,35-37,51-52,59,61-62,64-72,74-76,84,92-93,100-103,105-109H,22,30-34,91H2,1-7H3,(H2,90,104)(H,94,114)(H,95,111)(H,96,113)(H,97,115)(H,98,110)(H,99,112)(H,116,117)2*(H3,1,2,3,4)/t36-,37-,51+,52-,59+,61-,62-,64+,65+,66-,67+,68-,69+,70+,71-,72+,74+,75-,76-,84-,85-,86-/m0../s1
|
| Chemical Name |
(4R)-22-O-(3-Amino-2,3,6-trideoxy-3-C-methyl-α-L-arabinohexopyranosyl)-N3-(p-(p-chlorophenyl)benzyl)vancomycin diphosphate
|
| Synonyms |
Oritavancin Free Base; LY333328; LY 333328; 171099-57-3; LY333328; Chlorobiphenyl-chloroeremomycin; Oritavancin [INN]; LY-333328; UNII-PUG62FRZ2E; PUG62FRZ2E; LY-333328
|
| 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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.5577 mL | 2.7885 mL | 5.5769 mL | |
| 5 mM | 0.1115 mL | 0.5577 mL | 1.1154 mL | |
| 10 mM | 0.0558 mL | 0.2788 mL | 0.5577 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.