 Chemical Structure.png)
Sulbactam (CP 45899 and Betamaze) is a potent and irreversible β-lactamase inhibitor given in combination with β-lactam antibiotics to inhibit β-lactamase, an enzyme produced by bacteria that destroys antibiotic activity. It binds to the enzyme and prevent it to degrade the antibiotic.Sulbactam is able to inhibit the most common forms of β-lactamase but is not able to interact with the AmpC cephalosporinase. Thus, it confers little protection against bacteria such as Pseudomonas aeruginosa, Citrobacter, Enterobacter, and Serratia, which often express this gene.
Physicochemical Properties
| Molecular Formula | C8H11NO5S |
| Molecular Weight | 233.2416 |
| Exact Mass | 233.035 |
| Elemental Analysis | C, 41.20; H, 4.75; N, 6.01; O, 34.30; S, 13.75 |
| CAS # | 68373-14-8 |
| Related CAS # | Sulbactam sodium;69388-84-7 |
| PubChem CID | 130313 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.6±0.1 g/cm3 |
| Boiling Point | 567.7±50.0 °C at 760 mmHg |
| Melting Point | 146-151ºC |
| Flash Point | 297.1±30.1 °C |
| Vapour Pressure | 0.0±3.4 mmHg at 25°C |
| Index of Refraction | 1.605 |
| LogP | -1.39 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 15 |
| Complexity | 446 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | S1([C@]2([H])C([H])([H])C(N2[C@@]([H])(C(=O)O[H])C1(C([H])([H])[H])C([H])([H])[H])=O)(=O)=O |
| InChi Key | FKENQMMABCRJMK-RITPCOANSA-N |
| InChi Code | InChI=1S/C8H11NO5S/c1-8(2)6(7(11)12)9-4(10)3-5(9)15(8,13)14/h5-6H,3H2,1-2H3,(H,11,12)/t5-,6+/m1/s1 |
| Chemical Name | (2S,5R)-3,3-Dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid 4,4-dioxide |
| Synonyms | CP-45899; CP 45899; CP45899; CP-45,899; CP 45,899; CP45,899; Sulbactam |
| 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
| Targets | β-lactam |
| ln Vitro | Sulbactam exhibits broad spectrum antibacterial activity against both aerobic and anaerobic Gram-positive and Gram-negative bacteria[3]. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Sulbactam is poorly absorbed after oral administration. Peak serum concentrations of ampicillin and sulbactam are reached following a 15-minute intravenous infusion. After the intravenous administration of 2000 mg of ampicillin plus 1000 mg sulbactam, peak sulbactam serum levels corresponded to 48 to 88 mcg/mL. After the intravenous administration of 1000 mg ampicillin plus 500 mg sulbactam, peak sulbactam serum levels corresponded to 21 to 40 mcg/mL. After an intramuscular injection of 1000 mg ampicillin plus 500 mg sulbactam, peak sulbactam serum levels ranged from 6 to 24 mcg/mL. When given in combination with ampicillin in individuals with normal renal function, approximately 75 to 85% of the drug is excreted unchanged in the urine during the first eight hours after administration. The steady-state volumes of distribution range from 12.2 to 16.3 L. Sulbactam exhibits extensive distribution in extracellular fluids and tissues. Penetration of sulbactam into cerebrospinal fluid is enhanced in the presence of inflamed meninges. Eenal clearance is approximately 12 L/h following infusion over 15 to 30 minutes. Metabolism / Metabolites Metabolism of sulbactam has not been characterized. Biological Half-Life In healthy volunteers, the half-life is approximately one hour. |
| Toxicity/Toxicokinetics |
Protein Binding Sulbactam is approximately 38% reversibly bound to plasma proteins. |
| References |
[1]. Sulbactam: a beta-lactamase inhibitor. Clin Pharm. 1988;7(1):37-51. [2]. Sulbactam treatment for pneumonia involving multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex. Infect Dis (Lond). 2015;47(6):370-378. [3]. Ampicillin-sulbactam: an update on the use of parenteral and oral forms in bacterial infections. Expert Opin Drug Metab Toxicol. 2009;5(9):1099-1112. [4]. J Infect Dis, 1993. 167(2): p. 448-51. [5]. J Antimicrob Chemother, 1998. 42(6): p. 793-802. |
| Additional Infomation |
Sulbactam is a member of penicillanic acids. It is a conjugate acid of a sulbactam(1-). Sulbactam is a beta (β)-lactamase inhibitor and a derivative of the basic penicillin nucleus. When given in combination with β-lactam antibiotics, sulbactam produces a synergistic effect as it blocks the enzyme responsible for drug resistance by hydrolyzing β-lactams. Sulbactam is a beta Lactamase Inhibitor. The mechanism of action of sulbactam is as a beta Lactamase Inhibitor. Sulbactam is a semi-synthetic beta-lactamase inhibitor. The beta-lactam ring of sulbactam irreversibly binds to beta-lactamase at or near its active site, thereby blocking enzyme activity and preventing metabolism of other beta-lactam antibiotics by the enzyme. Combining this agent with a beta-lactamase susceptible antibiotic, such as penicillins or a cephalosporin, to treat infections caused by beta-lactamase producing organisms, results in a decreased turnover rate of the beta-lactamase sensitive antibiotic and enhances its antibacterial activity. A beta-lactamase inhibitor with very weak antibacterial action. The compound prevents antibiotic destruction of beta-lactam antibiotics by inhibiting beta-lactamases, thus extending their spectrum activity. Combinations of sulbactam with beta-lactam antibiotics have been used successfully for the therapy of infections caused by organisms resistant to the antibiotic alone. See also: Sulbactam Sodium (has salt form); Sulbactam Pivoxil (is active moiety of); Sulbactam Benzathine (is active moiety of). Drug Indication Sulbactam is used in combination with other antibacterial agents. With [ampicillin], it is used to treat skin and skin structure infections, intra-abdominal infections, and gynecological infections caused by susceptible bacteria. In combination with [durlobactam], sulbactam is indicated in adults for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), caused by susceptible isolates of _Acinetobacter baumannii-calcoaceticus_ complex. FDA Label Mechanism of Action Sulbactam is a competitive, irreversible bacterial beta (β)-lactamase inhibitor. It is reported to be more potent against class C beta-lactamases. Pharmacodynamics When given together with beta-lactam antibiotics, sulbactam broadens their antibacterial spectrum by blocking the enzyme involved in their hydrolysis. Sulbactam alone possesses weak intrinsic antibacterial activity except against the _Neisseriaceae_, _Acinetobacter spp._, and _Bacteroides fragilis_ as it can bind to the penicillin-binding proteins. Sulbactam restores the activity of beta-lactam antibiotics against a range of beta-lactamase-producing gram-positive and gram-negative bacteria. |
Solubility Data
| Solubility (In Vitro) |
DMSO : 47~100 mg/mL ( 201.5~428.74 mM ) Water : 20~47 mg/mL(85.75 mM) Ethanol : ~47 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.72 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 (10.72 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (10.72 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. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (10.72 mM) Solubility in Formulation 5: 100 mg/mL (428.74 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2874 mL | 21.4371 mL | 42.8743 mL | |
| 5 mM | 0.8575 mL | 4.2874 mL | 8.5749 mL | |
| 10 mM | 0.4287 mL | 2.1437 mL | 4.2874 mL |