| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Imipenem targets bacterial penicillin-binding proteins (PBPs) to inhibit cell wall synthesis. Cilastatin targets renal dehydropeptidase-I (DPHP-I), a brush border enzyme that hydrolyzes and inactivates imipenem. By competitively and reversibly inhibiting DPHP-I, cilastatin protects imipenem from renal metabolism. Cilastatin also inhibits leukotriene D4 dipeptidase, reducing conversion of leukotriene D4 to leukotriene E4. No off-target cross-resistance exists between imipenem/cilastatin and quinolone, aminoglycoside, macrolide or tetracycline classes.
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| ln Vitro |
Imipenem exhibits potent broad-spectrum in vitro antibacterial activity against Gram-positive and Gram-negative bacteria including obligate anaerobes. MIC values: ≤0.39 microg/mL for Staphylococcus aureus, ≤3.13 microg/mL for Proteus mirabilis, 1.56 microg/mL peak for Pseudomonas aeruginosa. MIC80 against S. aureus and S. epidermidis are 25 and 1.56 microg/mL respectively. Imipenem is stable to hydrolysis by most beta-lactamases including penicillinases and cephalosporinases. In vitro tests show synergy with aminoglycosides against some P. aeruginosa isolates.
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| ln Vivo |
In vivo animal studies in rats receiving IV imipenem/cilastatin at doses up to 600/600 mg/kg/day for 21 days showed no nephrotoxicity. No potentiation of furosemide- or glycerol-induced nephrotoxicity was observed. In dogs, young puppies and rabbits, IV administration at 10 mg/kg showed good tolerability. In rabbit EEG arousal threshold assays, 50 mg/kg IV caused no effect; 200 mg/kg imipenem slightly increased threshold by ~23%. Cilastatin at 25 mg/kg produced mild temperature decrease in rats; at 100 mg/kg increased locomotor activity.
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| Enzyme Assay |
Prepare pure imipenem/cilastatin sodium in PBS pH 7.4 at 1 mg/mL. Perform agar dilution method with inoculum of 10⁶ CFU/mL bacteria on Mueller-Hinton agar plates. Add compound at serial two-fold dilutions (0.125-128 microg/mL). Incubate plates at 35+/-2degC for 18-24 h. MIC is lowest concentration with no visible bacterial growth. For dehydropeptidase-I inhibition, incubate purified DPHP-I enzyme (1 U/mL) with imipenem (100 microM) +/- cilastatin (0.1-100 microM) in 50 mM Tris-HCl pH 8.0 at 37degC for 30 min. Measure remaining imipenem by HPLC. Calculate % inhibition.
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| Cell Assay |
Not a cell-based assay as this is an antibacterial drug. For MIC determination, bacterial cells (e.g., S. aureus, E. coli, P. aeruginosa) are cultured overnight in Mueller-Hinton broth, then diluted to 10⁵-10⁶ CFU/mL. Inoculate 96-well plates with 100 microL bacterial suspension per well. Add imipenem/cilastatin at two-fold dilutions (0.125-128 microg/mL) in triplicate. Incubate at 35+/-2degC for 18-24 h. Read MIC as lowest concentration inhibiting visible growth. Positive control: ciprofloxacin; negative control: broth only. Synergy testing with aminoglycosides: checkerboard method with fractional inhibitory concentration index calculation.
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| Animal Protocol |
In murine thigh infection models, female ICR mice (18-22 g, n=5/group) are infected intramuscularly with 10⁶ CFU P. aeruginosa or S. aureus. Imipenem/cilastatin is administered IV at 25-100 mg/kg q4h for 24 h. After treatment, thigh muscles are harvested, homogenized, and plated on agar. Colony counts are compared with untreated controls. Efficacy = log CFU reduction. In rat peritonitis models, male Wistar rats are infected IP with E. coli. Compound is given IV 1 h post-infection, survival monitored for 72 h. Rats tolerate IV doses up to 600 mg/kg/day for 21 days without toxicity.
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| ADME/Pharmacokinetics |
When given IV to healthy volunteers, imipenem/cilastatin shows linear PK across therapeutic dose range. Peak plasma levels for 500 mg/500 mg: 21-58 microg/mL (imipenem), 31-49 microg/mL (cilastatin). t½ = 1 h for both agents. Vd ~0.23-0.31 L/kg. Serum protein binding ~20% for imipenem. Urinary recovery: imipenem 70%, cilastatin 70-80%. CL ~200 mL/min. No accumulation with repeated dosing. Decreased renal function (GFR <30 mL/min/1.73m2) requires dose reduction. t½ prolonged to 2-4 h in renal impairment. In pediatric patients, PK similar to adults.
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| Toxicity/Toxicokinetics |
In rats, IV imipenem alone or with cilastatin (600 mg/kg/day for 21 days) showed no nephrotoxicity, unlike cephaloridine which induced proximal tubular damage. No potentiation of furosemide/glycerol-induced nephrotoxicity. Rabbit EEG: 200 mg/kg imipenem increased threshold ~23%. Common adverse effects in humans: GI upset (nausea, vomiting, diarrhea), injection site reactions. Hypersensitivity cross-reactivity with penicillins occurs in ~10% of penicillin-allergic patients. Seizures reported at high doses (>2 g/day), more common in CNS disorders. Contraindicated in patients hypersensitive to any component of the product.
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| References | |
| Additional Infomation |
The combination imipenem/cilastatin is marketed under brand name Primaxin. CAS: 85960-17-4. Molecular formula C28H43N5NaO9S2. MW 680.79. Supplied as sterile powder for injection containing sodium bicarbonate buffer. Reconstituted solution pH 6.5-8.5. Storage: 25degC, protect from freezing. Developed by Merck, approved by FDA in 1985. WHO essential medicine. Also used in veterinary medicine. Available as 250 mg, 500 mg, and 1 g vials. Compatible with D5W and NS. Not effective orally (must be IV). Pregnancy category C.
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| Molecular Formula |
C28H42N5NAO9S2
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| Molecular Weight |
679.78
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| Exact Mass |
679.232
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| CAS # |
85960-17-4
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| Related CAS # |
92309-29-0 (Parent)
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| PubChem CID |
23702788
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| Appearance |
Off-white to light yellow solid powder
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| Hydrogen Bond Donor Count |
6
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| Rotatable Bond Count |
17
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| Heavy Atom Count |
45
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| Complexity |
1020
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| Defined Atom Stereocenter Count |
5
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| SMILES |
C[C@H]([C@@H]1[C@H]2CC(=C(N2C1=O)C(=O)O)SCCN=CN)O.CC1(C[C@@H]1C(=O)N/C(=C\\CCCCSC[C@@H](C(=O)O)N)/C(=O)[O-])C.[Na+]
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| InChi Key |
VEVHCKVFLWYWCN-KJWPAVRRSA-M
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| InChi Code |
InChI=1S/C16H26N2O5S.C12H17N3O4S.Na/c1-16(2)8-10(16)13(19)18-12(15(22)23)6-4-3-5-7-24-9-11(17)14(20)21;1-6(16)9-7-4-8(20-3-2-14-5-13)10(12(18)19)15(7)11(9)17;/h6,10-11H,3-5,7-9,17H2,1-2H3,(H,18,19)(H,20,21)(H,22,23);5-7,9,16H,2-4H2,1H3,(H2,13,14)(H,18,19);/q;;+1/p-1/b12-6-;;/t10-,11+;6-,7-,9-;/m11./s1
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| Chemical Name |
sodium;(Z)-7-[(2R)-2-amino-2-carboxyethyl]sulfanyl-2-[[(1S)-2,2-dimethylcyclopropanecarbonyl]amino]hept-2-enoate;(5R,6S)-3-[2-(aminomethylideneamino)ethylsulfanyl]-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
H2O : ~20 mg/mL (~29.42 mM; with sonication)
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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 | 1.4711 mL | 7.3553 mL | 14.7106 mL | |
| 5 mM | 0.2942 mL | 1.4711 mL | 2.9421 mL | |
| 10 mM | 0.1471 mL | 0.7355 mL | 1.4711 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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