| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Polymyxin antibiotic
|
|---|---|
| Toxicity/Toxicokinetics |
Colistin did not exhibit significant genotoxic activity or carcinogenic structural warnings, was poorly absorbed in the gastrointestinal tract, and no tumors or precancerous lesions were observed in repeated oral or parenteral administration studies in rats over a period of 26 weeks. Therefore, the Committee concluded that colistin compounds are unlikely to be carcinogenic. The relevant endpoint for risk assessment was determined to be disruption of the colonic colonization barrier through toxicity to the gut microbiota, with Escherichia coli being the most susceptible. In vitro studies have shown that the minimum inhibitory concentration (MIC50) against 50% of E. coli strains is 1 µg/ml colistin base. Based on the MIC50 value of E. coli, the Committee converted the upper limit of ADI to 0–7 µg/kg body weight/day (420 µg/p/d for a 60 kg adult) using the following formula: ADI (µg/kg bw/d) = (MIC50 (1 µg/ml) × colonic contents mass (220 g)) / (bioavailability (0.5) × safety factor (1) × body weight (60 kg)). The committee recommends maximum residue limits (MRLs) of 150 µg/kg for colistin A+B in the liver, muscle, and fat (including applicable skin and fat) of cattle, sheep, goats, pigs, chickens, turkeys, and rabbits; 200 µg/kg for kidneys; 300 µg/kg for eggs; and 50 µg/kg for cow and sheep milk. The recommended MRLs result in a total daily intake (TMDI) of 229 µg (55% of the acceptable daily intake). Calculated upper limits for daily intake (EDIs) range from 4% (chicken) to 9% (cattle) of the EDI. The EDI of 56.9 µg (14% of the EDI) was calculated based on the highest median among the tissues and edible species.
|
| References |
[1]. Lauren M. Lim, et al. Resurgence of Colistin: A Review of Resistance, Toxicity, Pharmacodynamics, and Dosing. Pharmacotherapy. 2010 Dec; 30(12): 1279-1291.
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| Additional Infomation |
Colistin, a polymyxin antibiotic, was discovered in the late 1940s for the treatment of Gram-negative bacterial infections. After several years of clinical use, its use declined due to reports of significant nephrotoxicity and neurotoxicity. In recent years, colistin has regained attention as a last-line treatment for infections caused by multidrug-resistant bacteria such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. The high morbidity and mortality rates of these Gram-negative pathogens necessitate antibiotics that can cover them, making colistin a crucial treatment option. Unfortunately, case reports indicate that resistance to colistin has emerged in all three bacteria. While the exact mechanisms of colistin resistance are not fully understood, the PmrA-PmrB and PhoP-PhoQ gene regulatory systems are hypothesized to play a role. Because colistin is a last resort, its dosage must be optimized; furthermore, inadequate dosage is associated with the development of resistance. However, due to the lack of pharmacokinetic and pharmacodynamic studies and the lack of standardized dosage units, it is difficult to develop optimal dosing regimens and specific dosing guidelines for colistin. In critically ill patients who may experience multiple organ failure, renal insufficiency may alter the pharmacokinetics of colistin. Therefore, for these patients, the dosage must be adjusted to achieve the best efficacy and minimum toxicity. Regarding the toxicity of colistin, most studies have shown that nephrotoxicity is reversible and occurs less frequently than previously expected, while neurotoxicity is rare. Further research is needed to fully understand the impact of the two regulatory systems on resistance, and the colistin dosage required to inhibit and overcome these resistance patterns. [1]
|
| Molecular Formula |
C53H104N16O18S
|
|---|---|
| Molecular Weight |
1285.55
|
| Exact Mass |
1168.7655
|
| PubChem CID |
24825758
|
| Sequence |
{(+)-6-methyloctanoyl}-{Dab}-Thr-{Dab}-{Dab}-{Dab}-{D-Leu}-Leu-{Dab}-{Dab}-Thr (Lactam bridge:Dab-4-Thr-10)
|
| SequenceShortening |
{(+)-6-methyloctanoyl}-{Dab}T{Dab}{Dab}{Dab}{D-Leu}L{Dab}{Dab}T (Lactam bridge:Dab-4-Thr-10)
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
-2.8
|
| InChi Key |
XDJYMJULXQKGMM-HHAJOKTESA-N
|
| InChi Code |
InChI=1S/C53H100N16O13/c1-9-30(6)12-10-11-13-41(72)60-33(14-20-54)48(77)69-43(32(8)71)53(82)65-36(17-23-57)45(74)64-38-19-25-59-52(81)42(31(7)70)68-49(78)37(18-24-58)62-44(73)34(15-21-55)63-50(79)39(26-28(2)3)67-51(80)40(27-29(4)5)66-46(75)35(16-22-56)61-47(38)76/h28-40,42-43,70-71H,9-27,54-58H2,1-8H3,(H,59,81)(H,60,72)(H,61,76)(H,62,73)(H,63,79)(H,64,74)(H,65,82)(H,66,75)(H,67,80)(H,68,78)(H,69,77)/t30-,31+,32+,33-,34-,35-,36-,37-,38-,39-,40+,42-,43-/m0/s1
|
| Chemical Name |
(6S)-N-[(2S)-4-amino-1-[[(2S,3R)-1-[[(2S)-4-amino-1-oxo-1-[[(3S,6S,9S,12S,15R,18S,21S)-6,9,18-tris(2-aminoethyl)-3-[(1R)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]-6-methyloctanamide
|
| Synonyms |
Colistin A; 7722-44-3; UNII-500HI50Z9H; 500HI50Z9H; COLISTIN A [MI]; BRN 0604503; COLISTIN A [WHO-DD]; ...; Colistin A Sulfate Hydrate (~90%);
|
| 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)
|
| 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
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|---|---|
| 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 | 0.7779 mL | 3.8894 mL | 7.7788 mL | |
| 5 mM | 0.1556 mL | 0.7779 mL | 1.5558 mL | |
| 10 mM | 0.0778 mL | 0.3889 mL | 0.7779 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.
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