 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C80H106N11O27PCL2 |
| Exact Mass | 1753.64 |
| CAS # | 372151-71-8 |
| PubChem CID | 3081362 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 6.991 |
| Hydrogen Bond Donor Count | 23 |
| Hydrogen Bond Acceptor Count | 31 |
| Rotatable Bond Count | 30 |
| Heavy Atom Count | 121 |
| Complexity | 3490 |
| Defined Atom Stereocenter Count | 18 |
| SMILES | CCCCCCCCCCNCCN[C@]1(C[C@H](O[C@@H]2[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]2OC2=C3C=C4[C@H](C(N[C@@H]5C(=O)N[C@@H]([C@@H](C6=CC=C(OC2=C4)C(Cl)=C6)O)C(=O)N[C@H](C(=O)O)C2=CC(=C(C(O)=C2C2C(=CC=C5C=2)O)CNCP(=O)(O)O)O)=O)NC([C@@H](NC([C@@H]([C@@H](C2=CC=C(O3)C(Cl)=C2)O)NC([C@@H](CC(C)C)NC)=O)=O)CC(=O)N)=O)O[C@@H](C)[C@H]1O)C |c:53,66,73,t:104,&1:14,16,18,19,21,23,27,33,36,40,41,56,85,88,89,101,116,118| |
| InChi Key | ONUMZHGUFYIKPM-MXNFEBESSA-N |
| InChi Code | InChI=1S/C80H106Cl2N11O27P/c1-7-8-9-10-11-12-13-14-21-85-22-23-87-80(5)32-57(115-37(4)71(80)103)119-70-68(102)67(101)55(34-94)118-79(70)120-69-53-28-41-29-54(69)117-52-20-17-40(27-46(52)82)65(99)63-77(109)91-61(78(110)111)43-30-50(96)44(33-86-35-121(112,113)114)66(100)58(43)42-25-38(15-18-49(42)95)59(74(106)93-63)90-75(107)60(41)89-73(105)48(31-56(83)97)88-76(108)62(92-72(104)47(84-6)24-36(2)3)64(98)39-16-19-51(116-53)45(81)26-39/h15-20,25-30,36-37,47-48,55,57,59-65,67-68,70-71,79,84-87,94-96,98-103H,7-14,21-24,31-35H2,1-6H3,(H2,83,97)(H,88,108)(H,89,105)(H,90,107)(H,91,109)(H,92,104)(H,93,106)(H,110,111)(H2,112,113,114)/t37-,47+,48-,55+,57-,59+,60+,61-,62+,63-,64+,65+,67+,68-,70+,71+,79-,80-/m0/s1 |
| Chemical Name | (1S,2R,18R,19R,22S,25R,28R,40S)-22-(2-amino-2-oxoethyl)-5,15-dichloro-48-[(2S,3R,4S,5S,6R)-3-[(2S,4S,5S,6S)-4-[2-(decylamino)ethylamino]-5-hydroxy-4,6-dimethyloxan-2-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2,18,32,35,37-pentahydroxy-19-[[(2R)-4-methyl-2-(methylamino)pentanoyl]amino]-20,23,26,42,44-pentaoxo-36-[(phosphonomethylamino)methyl]-7,13-dioxa-21,24,27,41,43-pentazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25.034,39]pentaconta-3,5,8(48),9,11,14,16,29(45),30,32,34,36,38,46,49-pentadecaene-40-carboxylic acid |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| ln Vitro | Telavancin has a bactericidal effect that is quick and concentration-dependent because it breaks down the integrity of cell membranes [1]. At a dosage of 5 μg/mL, telavancin is bactericidal against MRSA strains (COL) and VISA strains (HIP5836) [1]. |
| ln Vivo | Telavancin has been investigated in different important animal models of infection, particularly bacteremia (40 mg/kg/d; subcutaneous injection; twice daily 12 hours apart), endocarditis (30 mg/ kg/d; intravenous injection; twice daily, 12 hours apart; 4 d), successfully treats meningitis and pneumonia [1] |
| Animal Protocol |
Animal/Disease Models: Neutropenic mouse MRSA bacteremia model [1] Doses: 40 mg /kg Route of Administration: subcutaneous injection; 20 mg/kg twice (two times) daily, 12 hrs (hrs (hours)) apart Experimental Results: 14-day survival rate was Dramatically improved compared to vancomycin-treated animals. Animal/Disease Models: Rabbit Staphylococcus aureus endocarditis model [1] Doses: 30 mg/kg Route of Administration: intravenous (iv) (iv)injection; twice a day, 12 hrs (hrs (hours)) apart, for 4 days Experimental Results: MRSA density in all target tissues was significant Dramatically diminished and increased the percentage of negative cultures in these organs. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Telavancin demonstrates linear pharmacokinetics at doses between 1 and 12.5 mg/kg. Furthermore, 24 hours post-infusion of a dose of 7.5 to 15 mg/kg, activity against MRSA and penicillin-resistant Streptococcus pneumonia can still be observed. The trough concentration at this point of time is approximately 10 μg/mL. Telavancin also has poor bioavailability and must be administered over 30-120 minutes IV. Cmax, healthy subjects, 10 mg/kg = 93.6 ± 14.2 μg/mL; AUC (0- ∞), healthy subjects, 10 mg/kg = 747 ± 129 μg · h/mL; AUC (0-24h), healthy subjects, 10 mg/kg = 666± 107 μg · h/mL; Time to steady state = 3 days; Urine with >80% as unchanged drug and <20% as hydroxylated metabolites (with dose of 10mg/kg); Feces (<1%) Vss, healthy subjects, 10 mg/kg = 0.14 L/kg Cl, healthy subjects, 10 mg/kg = 13.9 ± 2.9 mL/h/kg Telavancin is primarily eliminated by the kidney. In a mass balance study, approximately 76% of the administered dose was recovered from urine and <1% of the dose was recovered from feces (collected up to 216 hours) based on total radioactivity. Telavancin binds to human plasma proteins, primarily to serum albumin, in a concentration-independent manner. The mean binding is approximately 90% and is not affected by renal or hepatic impairment. Concentrations of telavancin in skin blister fluid were 40% of those in plasma (AUC0-24hr ratio) after 3 daily doses of 7.5 mg/kg VIBATIV in healthy young adults. The mass balance and pharmacokinetics of telavancin, a semisynthetic lipoglycopeptide antimicrobial agent, were characterized in an open-label, phase 1 study of six healthy male subjects. After a single 1-h intravenous infusion of 10 mg/kg (14)C-telavancin (0.68 uCi/kg), blood, urine, and feces were collected at regular intervals up to 216 hr postdose. Whole blood, plasma, urine, and fecal samples were assayed for total radioactivity using scintillation counting; plasma and urine were also assayed for parent drug and metabolites using liquid chromatography with tandem mass spectrometry. The concentration-time profiles for telavancin and total radioactivity in plasma were comparable from 0 to 24 hr after the study drug administration. Telavancin accounted for >95% and 83% of total radioactivity in plasma at 12 hr and 24 hr, respectively. By 216 hr, approximately 76% of the total administered dose was recovered in urine while only 1% was collected in feces. Unchanged telavancin accounted for most (83%) of the eliminated dose. Telavancin metabolite THRX-651540 along with two other hydroxylated metabolites (designated M1 and M2) accounted for the remaining radioactivity recovered from urine. The mean concentrations of total radioactivity in whole blood were lower than the concentration observed in plasma, and mean concentrations of THRX-651540 in plasma were minimal relative to mean plasma telavancin concentrations. These observations demonstrate that most of an administered telavancin dose is eliminated unchanged via the kidneys. ... The aim of this study was to assess the steady-state pharmacokinetic parameters of telavancin, an investigational bactericidal lipoglycopeptide, after intravenous (iv) administration to healthy male and female subjects. In a randomized, double-blind, parallel-group, gender-stratified, two-dose study, 79 adult subjects received three daily 60 min iv infusions of telavancin at 7.5 mg/kg (n = 40) or 15 mg/kg (n = 39). Blood and urine samples were collected for pharmacokinetic analyses at admission, on day 3 pre-infusion and up to 48 hr after the start of the day 3 infusion for 73 subjects (45 males and 28 females). Pharmacokinetic parameters were estimated by non-compartmental analysis. Following the day 3 telavancin dose (7.5 or 15 mg/kg), dose-proportional increases in mean peak plasma concentrations (C(max), 88 versus 186 mg/L for low and high doses, respectively) and total systemic exposures (AUC(0-24), 599 versus 1282 mg.h/L for low and high doses, respectively) were observed. Trough concentrations at steady state were 6 mg/L at 7.5 mg/kg/day and 16 mg/L at 15 mg/kg/day. The elimination half-life was dose-independent; the mean +/- SD ranged from 6.0 +/- 0.6 to 7.5 +/- 1.3 hr for low and high doses, respectively. Approximately two-thirds of the total telavancin dose was excreted unchanged in urine over 48 hr. Pharmacokinetic parameters were similar in males and females. Telavancin displayed linear plasma pharmacokinetics over the dose range 7.5-15 mg/kg/day and was primarily cleared via urinary excretion. No gender-related differences in the pharmacokinetic disposition of telavancin were observed. These data further characterize the pharmacokinetic profile of telavancin, a once-daily therapy targeted for the treatment of serious Gram-positive infections. For more Absorption, Distribution and Excretion (Complete) data for Telavancin (8 total), please visit the HSDB record page. Metabolism / Metabolites Metabolism of telavancin does not involve the cytochrome P450 enzyme system. Primary metabolite is called THRX-651540, but the metabolite pathway has not been identified. In a mass balance study in male subjects using radiolabeled telavancin, 3 hydroxylated metabolites were identified with the predominant metabolite (THRX-651540) accounting for <10% of the radioactivity in urine and <2% of the radioactivity in plasma. The metabolic pathway for telavancin has not been identified. No metabolites of telavancin were detected in in vitro studies using human liver microsomes, liver slices, hepatocytes, and kidney S9 fraction. None of the following recombinant CYP 450 isoforms were shown to metabolize telavancin in human liver microsomes: CYP 1A2, 2C9, 2C19, 2D6, 3A4, 3A5, 4A11. Telavancin was not extensively metabolized in rats, dogs and monkeys after IV administration. Unchanged telavancin was the predominant component in the serum (99, 89 and 94 % of total AUC for rats, dogs and monkeys, respectively) while 7-OH-telavancin (AMI-11352), telavancin des-phosphonate (AMI-999) and other OH-metabolites were identified. Telavancin accounted for more than 60% (dogs) and 86% (monkeys) of the urinary recoveries. AMI-11352 represented about 17% (dogs) and 5% (monkeys) of total urinary recovery while AMI-999 represented about 1.2% (dogs) and 1.8% (monkeys) and other OH-metabolites represented about 17% (dogs) and 6% (monkey). There was no significant gender-related difference observed for metabolism profiles. Of the three OH-metabolites of the 2-(decylamino) ethyl side chain of telavancin identified in human urine 7-OH-telavancin (AMI-11352) was the most abundant. The plasma AUC of 7-OH-telavancin (which is much less active against bacteria than telavancin) was about 2-3% of the AUC of telavancin and accounted for 50% of total peak areas of the three hydroxylated metabolites. AMI-11355 (8-OH metabolite) and AMI-11353 (9-OH metabolite) accounted for 24.2% and 25.3% of the total peak areas of the three hydroxylated metabolites, respectively. Plasma concentrations of AMI-11352 were low in the rat and increases in Cmax and AUC0-24 were less than dose-proportional. Systemic exposure to AMI-11352 was larger in dogs compared to rats. According to the applicant, saturation of the metabolic pathway at higher doses may be anticipated as the AUC0-t metabolite/telavancin ratio decreased at high doses in both rats and dogs. Systemic exposures to telavancin, AMI-999 and AMI-11352 in rats and/or dogs at steady state exceeded human systemic exposure at the proposed clinical dose of 10 mg/kg/day. The main metabolite of telavancin, 7-OH-Telavancin (AMI-11352), has antibacterial activity but is 10-fold less potent than telavancin. Due to the low antibacterial activity of AMI-11352 and the low human exposure, this metabolite is not considered to have a relevant contribution to the overall activity of telavancin in vivo. Biological Half-Life Terminal elimination half-life = 8 ± 1.5 hours (with normal renal function) Following single doses of 10 mg/kg telavancin (IV bolus injection or infusion) the serum or plasma concentrations of telavancin declined in all species with half life ranging from 1.2 hours in mice to 2.3 hours in monkeys. In a randomized, double-blind, parallel-group, gender-stratified, two-dose study, 79 adult subjects received three daily 60 min iv infusions of telavancin at 7.5 mg/kg (n = 40) or 15 mg/kg (n = 39). Blood and urine samples were collected for pharmacokinetic analyses at admission, on day 3 pre-infusion and up to 48 hr after the start of the day 3 infusion for 73 subjects (45 males and 28 females). ... The elimination half-life was dose-independent; the mean +/- SD ranged from 6.0 +/- 0.6 to 7.5 +/- 1.3 hr for low and high doses, respectively. ... In the pigmented rat quantitative whole body autoradiography (QWBA) study the highest levels of radioactivity at 168 hours post dose were observed in liver, spleen and kidney and at 336 hours post dose were observed in spleen, adrenal gland and kidney. The half-life estimated for liver and kidney were 4 and 5 days, respectively. The high levels of radioactivity observed in the bone at all time points appeared to be mainly located in the growth plates and also in the bone marrow with an estimated half-life of 332 hours (approximately 14 days). Penetration into the CNS was minimal. |
| Toxicity/Toxicokinetics |
Toxicity Summary IDENTIFICATION AND USE: Telavancin is off-white to slightly colored amorphous powder that is formulated into a solution for IV injection. Telavancin, a lipoglycopeptide antibacterial, is a synthetic derivative of vancomycin. It is used for the treatment of complicated skin and skin structure infections. Telavancin is also used for the treatment of adult patients with hospital-acquired and ventilator associated bacterial pneumonia. The US Food and Drug Administration approved a Risk Evaluation and Mitigation Strategy (REMS) for telavancin to prevent unintended telavancin exposure in pregnant women. HUMAN EXPOSURE AND TOXICITY: Women should avoid the use of telavancin during pregnancy unless the potential benefit outweighs the potential risk to the fetus. Furthermore, women of childbearing potential should have a serum pregnancy test prior to administration of telavancin. Also, patients with pre-existing moderate to severe renal impairment had increased mortality observed versus vancomycin in clinical trials. Therefore, use of telavancin in such patients should be considered only when the anticipated benefit to the patient outweighs the potential risk. Prolongation of the corrected QT interval (QTc) has also been reported in individuals receiving telavancin. Telavancin should therefore be avoided in individuals with congenital long QT syndrome, known prolongation of the QTc interval, uncompensated heart failure, or severe left ventricular hypertrophy. Finally, serious and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have occurred in patients following the first or subsequent doses of telavancin. ANIMAL STUDIES: The toxicity of repeated infusion of telavancin was investigated for up to three months in dogs and up to six months in rats at doses of up to 25 mg/kg/day. In the liver, treatment for 13 weeks or longer resulted in reversible degeneration/necrosis of hepatocytes accompanied by elevations in serum liver enzymes in both rats and dogs. Effects on the kidney of rats and dogs occurred after a minimum of 4 weeks of dosing and were a combination of renal tubular injury and tubular epithelial vacuolization. The tubular injury was characterized by degeneration and necrosis of proximal tubular cells, and was associated with increases in creatinine that reach a maximum of 2 times the control values at the highest doses. The tubular injury was reversible, but not all animals had reached full recovery 4 weeks after the end of treatment. In embryo-fetal development studies in rats, rabbits, and minipigs, telavancin demonstrated the potential to cause limb and skeletal malformations when given intravenously during the period of organogenesis at doses up to 150, 45, or 75 mg/kg/day, respectively. Malformations observed at <1% (but absent or at lower rates in historical or concurrent controls), included brachymelia (rats and rabbits), syndactyly (rats, minipigs), adactyly (rabbits), and polydactyly (minipigs). Additional findings included flexed front paw and absent ulna in rabbits, and misshapen digits and deformed front leg in the minipigs. Fetal body weights were decreased in rats. In a prenatal/perinatal development study, pregnant rats received intravenous telavancin at up to 150 mg/kg/day from the start of organogenesis through lactation. Offspring showed decreases in fetal body weight and an increase in the number of stillborn pups. Brachymelia was also observed. Neither mutagenic nor clastogenic potential of telavancin was found in a battery of tests including: assays for mutagenicity (Ames bacterial reversion), an in vitro chromosome aberration assay in human lymphocytes, and an in vivo mouse micronucleus assay. Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Telavancin is 93% plasma protein bound and is poorly absorbed orally, so it is not likely to reach the bloodstream of the infant or cause any adverse effects in breastfed infants. If telavancin is required by the mother, it is not a reason to discontinue breastfeeding. Monitor the infant for possible effects on the gastrointestinal tract, such as diarrhea, vomiting, and candidiasis (e.g., thrush, diaper rash). ◉ 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 >90% to serum albumin in a concentration independent manner (despite being highly protein bound, antimicrobial activity of telavancin is not affected) Interactions Adverse renal effects are more likely to occur in patients ... receiving concomitant therapy with an agent that affects renal function (eg, nonsteroidal anti-inflammatory agents (NSAIAs), certain diuretics, angiotensin-converting enzyme (ACE) inhibitors). |
| References | [1]. Das B, et al. Telavancin: a novel semisynthetic lipoglycopeptide agent to counter the challenge of resistant Gram-positive pathogens. Ther Adv Infect Dis. 2017 Mar;4(2):49-73. |
| Additional Infomation |
Therapeutic Uses Anti-Bacterial Agents Vibativ is indicated for the treatment of adult patients with complicated skin and skin structure infections (cSSSI) caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and -resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group (includes S. anginosus, S. intermedius, and S. constellatus), or Enterococcus faecalis (vancomycin-susceptible isolates only). /Included in US product label/ Vibativ is indicated for the treatment of adult patients with hospital-acquired and ventilator associated bacterial pneumonia (HABP/VABP), caused by susceptible isolates of 45 Staphylococcus aureus (including methicillin-susceptible and -resistant isolates). Vibativ 46 should be reserved for use when alternative treatments are not suitable. /Included in US product label/ The US Food and Drug Administration (FDA) required and approved a Risk Evaluation and Mitigation Strategy (REMS) for telavancin. The goal of the telavancin REMS is to avoid unintended telavancin exposure in pregnant women by educating health-care providers and patients about the potential risk of fetal developmental toxicity and recommended measures to exclude and prevent pregnancy. The REMS requires that a telavancin medication guide be provided to the patient each time the drug is dispensed and outlines a communication plan requiring initial and periodic communications from the manufacturer to certain targeted groups of prescribers and pharmacists. To reduce development of drug-resistant bacteria and maintain effectiveness of telavancin and other antibacterials, the drug should be used only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria. When selecting or modifying anti-infective therapy, results of culture and in vitro susceptibility testing should be used. In the absence of such data, local epidemiology and susceptibility patterns should be considered when selecting anti-infectives for empiric therapy. If documented or presumed pathogens include gram-negative or anaerobic bacteria, concomitant use of an anti-infective active against such bacteria may be clinically indicated. Drug Warnings /BOXED WARNING/ WARNING: Patients with pre-existing moderate/severe renal impairment (CrCl .50 mL/min) who were treated with Vibativ for hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia had increased mortality observed versus vancomycin. Use of Vibativ in patients with pre-existing moderate/severe renal impairment (CrCl .50 mL/min) should be considered only when the anticipated benefit to the patient outweighs the potential risk. /BOXED WARNING/ WARNING: Nephrotoxicity: New onset or worsening renal impairment has occurred. Monitor renal function in all patients. /BOXED WARNING/ WARNING: Women of childbearing potential should have a serum pregnancy test prior to administration of Vibativ. Avoid use of Vibativ during pregnancy unless potential benefit to the patient outweighs potential risk to the fetus. Adverse developmental outcomes observed in 3 animal species at clinically relevant doses raise concerns about potential adverse developmental outcomes in humans. Use of telavancin may result in overgrowth of nonsusceptible organisms, including fungi. The patient should be carefully monitored and appropriate therapy should be instituted if a superinfection occurs. Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile. C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) have been reported with nearly all anti-infectives and may range in severity from mild diarrhea to fatal colitis. C. difficile produces toxins A and B which contribute to development of CDAD; hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since these infections may be refractory to anti-infective therapy and may require colectomy. CDAD should be considered in the differential diagnosis of patients who develop diarrhea during or after anti-infective therapy. Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued. If CDAD is suspected or confirmed, anti-infective therapy not directed against C. difficile should be discontinued whenever possible. Patients should be managed with appropriate supportive therapy (fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated. For more Drug Warnings (Complete) data for Telavancin (18 total), please visit the HSDB record page. Pharmacodynamics Telavancin is a semi-synthetic derivative of vancomycin, therefore the mode of bactericidal action is similar to vancomycin in which both antibiotics inhibit cell wall synthesis. Not only that, it displays concentration-dependent bactericidal action. Furthermore, telavancin is a more potent inhibitor (10-fold) of peptidoglycan synthesis and, unlike vancomycin, disrupts cell membrane integrity via its interaction with lipid II. AUC/MIC ratio best predicts the extent of in-vivo response in which the higher the ratio, the greater the bactericidal activity. The smallest ratio in which one would be able to observe no bacterial growth at 24 hours is 50. Maximal bactericidal activity is observed at a AUC/MIC ratio of 404. |
Solubility Data
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |