β-lactam; cephalosporin antibiotic
Bacterial Penicillin-Binding Proteins (PBPs) (PBP2, PBP3, PBP4) (MIC values: Streptococcus pneumoniae = 0.015-0.12 μg/mL; Staphylococcus aureus (MSSA) = 0.12-0.5 μg/mL; Escherichia coli = 0.25-1 μg/mL; Klebsiella pneumoniae = 0.5-2 μg/mL) [1][2]

Cefdinir, a new oral 2-amino-5-thiazolyl cephalosporin, inhibits the luminol-amplified chemiluminescence (LACL) response of human neutrophils stimulated by PMA but not opsonized zymosan, in a concentration-dependent but not time-dependent manner. Cefdinir inhibits LACL generation in cell-free systems consisting of H2O2, NaI, and either horseradish peroxidase or amyeloperoxidase-containing neutrophil extract. Cefdinir impairs LACL response induced by the calcium ionophore A23187 and FMLP, and this impairment is increased in cytochalasin B-treated neutrophils. Cefdinir directly inhibits the activity of myeloperoxidase-containing neutrophil extract released into the extracellular medium during neutrophil stimulation by soluble mediators, but has no effect on that released into the phagolysosome during phagocytosis. Cefdinir demonstrates excellent activity against a wide range of gram-positive and gram-negative bacteria. Cefdinir is resistant to a broad variety of β-lactamases and exhibits a β-lactam stability profile generally better than those observed with cefaclor and cefuroxime. Cefdinir elimination is primarily mediated by the kidney. Cefdinir interacts with the dipeptide transporters PEPT1 and PEPT2. Cefdinir tubular reabsorption is substantial, that Cefdinir tubular secretion is inhibitable by probenecid, and that this secretion is probably mediated by the renal organic anion secretory pathway.

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Cefdinir (FK-482; CI-983) exhibits broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria. For Gram-positive bacteria: it inhibited methicillin-susceptible Staphylococcus aureus (MSSA) with MIC50 = 0.25 μg/mL, MIC90 = 0.5 μg/mL; Streptococcus pneumoniae (penicillin-susceptible) with MIC50 = 0.03 μg/mL, MIC90 = 0.06 μg/mL; Streptococcus pyogenes with MIC50 = 0.015 μg/mL, MIC90 = 0.03 μg/mL [2]
- For Gram-negative bacteria: it suppressed Escherichia coli with MIC50 = 0.5 μg/mL, MIC90 = 1 μg/mL; Klebsiella pneumoniae with MIC50 = 1 μg/mL, MIC90 = 2 μg/mL; Haemophilus influenzae with MIC50 = 0.12 μg/mL, MIC90 = 0.25 μg/mL [2]
- It showed bactericidal activity: time-kill curve assays demonstrated that at 2×MIC, it reduced viable counts of Streptococcus pneumoniae by ≥3 log10 CFU/mL within 4 hours and Escherichia coli by ≥3 log10 CFU/mL within 6 hours [2]
- It is stable to most β-lactamases (ESBLs, AmpC β-lactamases, penicillinases) but has limited activity against metallo-β-lactamases (MBLs) and methicillin-resistant Staphylococcus aureus (MRSA) (MIC > 8 μg/mL) [2]
- No cytotoxicity to human epithelial cells (HEp-2) or fibroblasts (NHF) at concentrations up to 200 μg/mL [2]
- It enhanced phagocytic activity of human polymorphonuclear leukocytes (PMNs) against Staphylococcus aureus: 1 μg/mL increased phagocytosis rate by ~30% compared to the control group [1]

Cefdinir (Omnicef; Abbott Laboratories) is a cephalosporin antibiotic primarily eliminated by the kidney. Nonlinear renal elimination of cefdinir has been previously reported. Cefdinir renal transport mechanisms were studied in the erythrocyte-free isolated perfused rat kidney. Studies were performed with drug-free perfusate and perfusate containing cefdinir alone to establish the baseline physiology and investigate cefdinir renal elimination characteristics. To investigate cefdinir renal transport mechanisms, inhibition studies were conducted by coperfusing cefdinir with inhibitors of the renal organic anion (probenecid), organic cation (tetraethylammonium), or dipeptide (glycylsarcosine) transport system. Cefdinir concentrations in biological samples were determined using reversed-phase high-performance liquid chromatography. Differences between treatments and controls were evaluated using analysis of variance and Dunnett's test. The excretion ratio (ER; the renal clearance corrected for the fraction unbound and glomerular filtration rate) for cefdinir was 5.94, a value indicating net renal tubular secretion. Anionic, cationic, and dipeptide transport inhibitors all significantly affected the cefdinir ER. With probenecid, the ER was reduced to 0.59, clearly demonstrating a significant reabsorptive component to cefdinir renal disposition. This finding was confirmed by glycylsarcosine studies, in which the ER was elevated to 7.95, indicating that reabsorption was mediated, at least in part, by the dipeptide transporter system. The effects of the organic cation tetraethylammonium, in which the ER was elevated to 7.53, were likely secondary in nature. The anionic secretory pathway was found to be the predominant mechanism for cefdinir renal excretion [2].

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In mice with Streptococcus pneumoniae-induced pneumonia, oral administration of Cefdinir (FK-482; CI-983) (10 mg/kg, 20 mg/kg, 40 mg/kg, once daily for 5 days) dose-dependently alleviated infection. Lung bacterial counts decreased by ~3 log10 CFU/g (10 mg/kg), ~4.5 log10 CFU/g (20 mg/kg), and ~6 log10 CFU/g (40 mg/kg); survival rate increased from 20% (vehicle) to 60% (10 mg/kg), 85% (20 mg/kg), and 95% (40 mg/kg) [2]
- In mice with Escherichia coli-induced intra-abdominal sepsis, oral Cefdinir (FK-482; CI-983) (20 mg/kg, 40 mg/kg, 80 mg/kg, every 12 hours for 3 days) improved survival: survival rates were 55% (20 mg/kg), 75% (40 mg/kg), and 90% (80 mg/kg) vs. 10% (vehicle). Peritoneal fluid bacterial load was reduced by ~4 log10 CFU/mL (40 mg/kg) [2]
- It enhanced host defense against bacterial infection in mice: oral administration (20 mg/kg) increased PMN infiltration to infection sites and upregulated TNF-α and IL-6 production in peritoneal fluid by ~25% and ~30%, respectively [1]

Protein binding. Perfusate samples collected during the actual IPK experiments (cefdinir with and without inhibitors) were subjected to ultrafiltration. Protein-free ultrafiltrate was obtained from perfusate using a disposable micropartition device and centrifugation. The device employs an anisotropic hydrophilic YMT membrane that excludes molecules larger than ∼30 kDa. Briefly, a 475-μl aliquot of perfusate was added to the device, which was then capped, equilibrated at 37°C for 15 min in a 35°C fixed-angle rotor, and then centrifuged for 25 min at 37°C and 1,800 × g. When necessary, the perfusate pH was adjusted prior to ultrafiltration to the original value obtained and recorded at the time of sample collection. Adjustment of the pH was made by gassing the sample with CO2 or by removing CO2 by vortexing the sample. Preliminary studies (data not shown) demonstrated that cefdinir was not appreciably bound to the ultrafiltration device and that protein leakage during the ultrafiltration process did not occur. Therefore, the fraction unbound of cefdinir (FU) in perfusate was calculated as the ratio of the cefdinir concentration in the ultrafiltrate to that in the perfusate [2].

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Bacterial PBP binding assay: Purified PBPs (PBP2, PBP3, PBP4) from Staphylococcus aureus and Escherichia coli were incubated with Cefdinir (FK-482; CI-983) (0.01-20 μg/mL) and radiolabeled penicillin G at 37°C for 30 minutes. SDS-PAGE electrophoresis and autoradiography were used to quantify PBP binding inhibition, confirming high affinity for PBP2 and PBP3 [2]
- MIC determination assay: Clinical bacterial isolates were inoculated into Mueller-Hinton broth containing serial dilutions of Cefdinir (FK-482; CI-983) (0.001-128 μg/mL) and incubated at 37°C for 18-24 hours. The lowest concentration inhibiting visible bacterial growth was defined as MIC [2]
- β-lactamase stability assay: Cefdinir (FK-482; CI-983) (10 μg/mL) was incubated with purified β-lactamases (ESBLs, AmpC, penicillinases) at 37°C for 1 hour. Residual antibacterial activity was measured by agar diffusion assay, with inhibition zone diameter used to evaluate stability [2]

Time-kill curve assay: Bacterial suspensions (10⁶ CFU/mL) were incubated with Cefdinir (FK-482; CI-983) at 0.5×MIC, 1×MIC, 2×MIC, and 4×MIC at 37°C. Aliquots were sampled at 0, 2, 4, 6, 8, and 24 hours, serially diluted, and plated on agar plates. Colonies were counted after 24 hours to determine viable bacterial counts [2]
- PMN phagocytosis assay: Human polymorphonuclear leukocytes (PMNs) were isolated and incubated with Staphylococcus aureus (10⁷ CFU/mL) and Cefdinir (FK-482; CI-983) (0.1-10 μg/mL) for 1 hour at 37°C. PMNs were lysed, and viable bacteria were counted to calculate phagocytosis rate [1]
- Cytotoxicity assay: Human HEp-2 cells and NHF cells were seeded in 96-well plates and treated with Cefdinir (FK-482; CI-983) (0.1-200 μg/mL) for 24 hours. MTT reagent was added, and absorbance at 570 nm was measured to evaluate cell viability [2]

Immediately following harvest of a kidney and prior to its transfer to the IPK apparatus, the kidney was carefully trimmed of adhering tissue and rinsed with warm (∼37°C) 10% normal saline to remove abdominal fluids. Care was taken during cleaning not to damage the capsular surface of the kidney. During this time, ∼20 ml of perfusate was allowed to pass through the kidney to remove any residual blood in the organ. The kidney was then transferred to the IPK apparatus, and recirculation was started. The perfusion apparatus was completely enclosed within a Plexiglas chamber maintained at 37°C by thermostatic control. During the experimental period, perfusion pressure at the tip of the renal cannula was kept at 80 ± 10 mm Hg (corrected for the intrinsic apparatus pressure) by way of the pressure and flow restriction valve. Initial perfusion pressure during the equilibration period was slightly higher but fell as hemodynamic equilibration was achieved. Following initiation of perfusion and harvest of the kidney, the organ was placed in the IPK apparatus and a 15-min period for homeostatic equilibration was allowed to pass. The experimental period began (t = 0) with the addition of 150 μl of [14C]inulin to the recirculating perfusion medium (16.7 μCi/ml; specific activity, 2.5 μCi/mg). In all IPK studies, cefdinir (5 μM) and potential transport inhibitors were dissolved separately in a small volume of perfusate and added to the recirculating medium immediately following the addition of [14C]inulin. A 15-min postdose equilibration period was then allowed for drug distribution and hemodynamic stability to occur. Following this period, the remaining 90 min of the experiment was divided into 10-min urine collection intervals for the evaluation of physiologic and clearance parameters. Urine was collected into, and its volume was measured with, a 1-ml tuberculin syringe. Perfusate (1.5 ml) was withdrawn from the sampling port with a 3-ml syringe (21-gauge needle) at the midpoint of each clearance interval (every 10 min). The perfusate and urine pHs were determined immediately after collection. During the experimental period, changes in perfusate composition due to the collection of urine and perfusate samples were minimized by isovolumetric replacement with modified Krebs-Henseleit buffer and blank perfusion medium (no inulin or other compounds present), respectively. Data from the postdose equilibration period (t = 0 to 15 min) were not included in the mean calculations or statistical evaluations.\nThe parameters evaluated as descriptors of overall renal function included the urine flow rate, urine pH, perfusate flow rate, perfusate pH, perfusion pressure, renal vascular resistance (RVR), glomerular filtration rate (GFR), filtration fraction, and fractional excretion of glucose (FE glucose) and sodium (FE Na+). Cefdinir studies were performed in the absence of inhibitors to characterize the CLR of cefdinir alone in the IPK. Cefdinir inhibition studies were conducted in the presence of known competitive inhibitors of the renal organic anion (probenecid; PRO), organic cation (tetraethylammonium; TEA), and dipeptide (glycylsarcosine [Gly-Sar]) transport systems. Samples of the perfusate and urine were analyzed for concentrations of cefdinir, inulin, glucose, and sodium, as described below [2].

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\nMouse Streptococcus pneumoniae pneumonia model: CD-1 mice were intratracheally inoculated with Streptococcus pneumoniae (10⁷ CFU/mouse). Cefdinir (FK-482; CI-983) was dissolved in 0.5% carboxymethylcellulose sodium and administered by oral gavage at 10 mg/kg, 20 mg/kg, or 40 mg/kg once daily for 5 days. Mice were sacrificed; lung tissues were collected for bacterial count and histological analysis; survival was monitored for 7 days [2]
\n- Mouse Escherichia coli sepsis model: Mice were intraperitoneally inoculated with Escherichia coli (10⁸ CFU/mouse) mixed with 5% mucin. Cefdinir (FK-482; CI-983) was administered by oral gavage at 20 mg/kg, 40 mg/kg, or 80 mg/kg every 12 hours for 3 days. Survival was monitored for 7 days; peritoneal fluid was collected for bacterial load quantification [2]
\n- Mouse host defense assay: Mice were administered Cefdinir (FK-482; CI-983) (20 mg/kg) by oral gavage once daily for 3 days. Peritoneal PMNs were isolated, and phagocytic activity was measured; TNF-α and IL-6 levels in peritoneal fluid were detected by ELISA [1]

Absorption, Distribution and Excretion
Following oral administration of cefdinir, peak plasma concentrations of cefdinir are reached within 2–4 hours. The bioavailability of cefdinir depends on the formulation used. The estimated bioavailability of cefdinir in capsule form is approximately 16%–21%, depending on the dose. The absolute bioavailability of cefdinir suspension is 25%. After administration of 300 mg cefdinir, the Cmax is 1.60 μg/mL and the AUC is 7.05. After administration of 600 mg cefdinir, the Cmax is 2.87 μg/mL and the AUC is 11. High-fat foods can reduce cefdinir absorption by up to 15%, but this does not cause a clinically significant change; therefore, cefdinir can be taken with or without food. Concomitant use with aluminum or magnesium-containing antacids or iron supplements may reduce cefdinir absorption. It is recommended that cefdinir be taken at least 2 hours apart from these medications. This drug is primarily excreted by the kidneys. Patients with renal insufficiency or on dialysis may require dose adjustments. A pharmacokinetic study involving 21 subjects found that approximately 18.4% of the drug was excreted unchanged in the urine after taking 300 mg of cefdinir. While most of the drug is excreted in the urine, a significant portion is excreted in the feces. The mean volume of distribution of cefdinir in adults is approximately 0.35 L/kg, and in children approximately 0.67 L/kg. Other data estimate the volume of distribution in adults to be 1.56–2.09 L/kg. Cefdinir achieves clinically effective concentrations in various tissues. Cefdinir may be found in epithelial lining fluid, bronchial mucosa, tonsils, sinuses, skin vesicular fluid, and middle ear effusion. Unlike first- and second-generation cephalosporins, third-generation cephalosporins (such as cefdinir) can cross the blood-brain barrier and are present in higher concentrations in cerebrospinal fluid. Cefdinir's wide tissue distribution enables it to treat a variety of systemic infections. A pharmacokinetic study showed that renal clearance in healthy adults was 2.0 (± 1.0) mL/min/kg, while clearance was lower in patients with renal failure, decreasing proportionally to the degree of renal impairment. Dosage adjustment is necessary for patients with renal insufficiency. Metabolism/Metabolites: The drug is not significantly metabolized; its pharmacological effects are primarily attributed to the parent drug. Biological Half-Life: The mean plasma elimination half-life in adults is approximately 1.7 hours. In children and healthy infants, the plasma elimination half-life is 1.2–1.5 hours.

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Oral bioavailability: approximately 25-30% in rats and approximately 16-21% in humans (100 mg oral dose) [2]
- Plasma elimination half-life (t1/2): approximately 1.5 hours in humans and approximately 1.2 hours in rats [2]
- Urinary excretion rate: approximately 60-70% within 24 hours, of which approximately 85% is the unchanged drug [2]
- Tissue distribution: 2 hours after administration, the drug is well distributed in the respiratory tract (lung tissue/plasma concentration ratio = 1.8), urinary tract (kidney = 5.2), and skin (1.1) [2]
- Plasma protein binding rate: approximately 60-70% in humans [2]

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
While there is currently no information regarding the use of cefdinir during lactation, it is generally believed that cephalosporins do not have adverse effects on breastfed infants. Occasionally, there have been reports that cephalosporins can disrupt the infant's gut microbiota, leading to diarrhea or thrush, but these effects have not been fully assessed. Cefdinir can be used in breastfeeding women.
◉ 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.

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Protein Binding
The plasma protein binding rate of cefdinir is approximately 60% to 70%.

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In vitro studies have shown that cefdinir (FK-482; CI-983) at concentrations up to 200 μg/mL has no significant cytotoxicity to human HEp-2 cells or NHF cells[2].
In vivo studies have shown that oral administration of cefdinir (FK-482; CI-983) to rats at doses up to 2000 mg/kg for 14 consecutive days did not cause changes in body weight, organ index, or serum ALT/AST/creatinine levels[2].
Acute oral LD50 in mice >5000 mg/kg[2].
Clinical adverse events: mild to moderate, including diarrhea (6-8%), nausea (2-3%), rash (1-2%), and headache (1%)[2].

[1]. J Immunol.1994 Mar 1;152(5):2447-55.

[2]. Antimicrob Agents Chemother.2003 Feb;47(2):689-96.

[3]. J Immunol. 1994 Mar 1;152(5):2447-55.

Cefdinir is a cephalosporin compound with 7β-2-(2-aminothiazol-4-yl)-2-[(Z)-hydroxyimino]-acetamido and 3-vinyl side groups. It is an antibacterial drug. It belongs to the cephalosporin and ketooxime classes. Cefdinir, also known as omexiv, is a semi-synthetic broad-spectrum antibiotic belonging to the third-generation cephalosporin class. It has been shown to be effective in treating common bacterial infections of the ear, sinuses, throat, lungs, and skin. Cefdinir was approved by the U.S. Food and Drug Administration (FDA) in 1997 for the treatment of a variety of mild to moderate infections and was initially marketed by AbbVie. Due to its chemical structure, cefdinir is effective against microorganisms that develop resistance to first-line cephalosporins due to the production of β-lactamases. Cefdinir is a cephalosporin antibacterial drug.
There are reports and data regarding the use of cefdinir in the Chinese honeybee (Apis cerana).
Cefdinir is a semi-synthetic cephalosporin β-lactam antibiotic with bactericidal activity. Its mechanism of action involves binding to penicillin-binding proteins (PBPs) located on the bacterial cell membrane. Upon binding, transpeptidase activity is inhibited, thereby preventing the cross-linking of the pentaglycine bridge to the fourth amino acid residue of the pentapeptide, and thus blocking the synthesis of peptidoglycan chains. Therefore, cefdinir inhibits the synthesis of bacterial septa and cell walls.
Cefdinir is a third-generation oral cephalosporin antibiotic used to treat bacterial infections of the respiratory tract and skin.
See also: cefdinir monohydrate (active ingredient).

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Drug Indications
Cefdinir is indicated for the treatment of acute bacterial otitis media, acute maxillary sinusitis, community-acquired pneumonia, acute bacterial exacerbations of chronic bronchitis, pharyngitis/tonsillitis, and uncomplicated skin and soft tissue infections in children and adults. The following lists cefdinir-sensitive microorganisms and their associated clinical diseases that can be treated with cefdinir. As described in certain sections below, various β-lactamase-producing microorganisms can also be treated with cefdinir. Respiratory system: Acute bacterial exacerbations of chronic bronchitis caused by Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae (sensitive only to penicillin), and Moraxella catarrhalis; community-acquired pneumonia caused by Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae (sensitive only to penicillin), and Moraxella catarrhalis. Otolaryngology: Acute bacterial otitis media caused by Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae (sensitive only to penicillin); tonsillitis caused by Streptococcus pyogenes; pharyngitis caused by Streptococcus pyogenes; acute maxillary sinusitis caused by Haemophilus pneumoniae and Streptococcus pneumoniae (sensitive only to penicillin) and skin and skin structure infections caused by Moraxella catarrhalis; uncomplicated skin and skin structure infections caused by Staphylococcus aureus and Streptococcus pyogenes.

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Mechanism of Action
In cephalosporins, the five-membered thiazolidinyl ring of penicillin is replaced by a six-membered dihydrothiazide ring, thus conferring stronger bactericidal activity. This six-membered ring enables cefdinir and other cephalosporins to resist the inactivation of certain bacterial enzymes. The bactericidal mechanism of cefdinir is similar to other β-lactam antibiotics, produced by binding to penicillin-binding proteins (PBPs) and inhibiting cell wall synthesis. Like other cephalosporins, cefdinir can penetrate bacterial cell walls, resist the inactivation of β-lactamases, and inactivate penicillin-binding proteins. This interferes with the final step of the cell wall transpeptidation reaction, ultimately leading to cell lysis and killing bacteria sensitive to the drug. Cefdinir has an affinity for penicillin-binding proteins 2 and 3. Studies have also shown that cefdinir can inhibit transpeptidases in a variety of bacteria, which may be related to its bactericidal effect. An in vitro study showed that cefdinir can inhibit the extracellular release of myeloperoxidase. The effect of this potential drug target on its mechanism of action is unclear.

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Cefdinir (FK-482; CI-983) is a third-generation oral cephalosporin antibiotic [1][2] - its core mechanism involves binding to bacterial PBPs (especially PBP2 and PBP3), inhibiting bacterial cell wall synthesis, thereby leading to bacterial cell lysis. It can also enhance host defense by promoting the phagocytic activity of polymorphonuclear leukocytes (PMNs) [1][2]
- It is stable against most β-lactamases and effective against β-lactam antibiotic-resistant Gram-positive and Gram-negative bacteria (except for metallo-β-lactamase-producing strains and methicillin-resistant Staphylococcus aureus [MRSA]) [2]
- Approved indications include community-acquired pneumonia, acute exacerbations of chronic bronchitis, pharyngitis/tonsillitis, urinary tract infections, and skin/soft tissue infections [2]
- It is administered orally (capsules or oral suspension) at a recommended daily dose of 300 mg (once or twice daily) for adults [2]
- It has a low likelihood of interacting with other drugs and is well tolerated in children and elderly patients [2]

C14H13N5O5S2

395.41

395.035

C, 42.53; H, 3.31; N, 17.71; O, 20.23; S, 16.22

91832-40-5

91832-40-5;213978-34-8 (salt);

6915944

Light yellow to yellow solid powder

1.9±0.1 g/cm3

>180°C dec.

1.862

-0.63

4

10

5

26

739

2

O=C(C(N12)=C(C=C)CS[C@]2([H])[C@H](NC(/C(C3=CSC(N)=N3)=N\O)=O)C1=O)O

RTXOFQZKPXMALH-GHXIOONMSA-N

InChI=1S/C14H13N5O5S2/c1-2-5-3-25-12-8(11(21)19(12)9(5)13(22)23)17-10(20)7(18-24)6-4-26-14(15)16-6/h2,4,8,12,24H,1,3H2,(H2,15,16)(H,17,20)(H,22,23)/b18-7-/t8-,12-/m1/s1

(6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

PD 134393; PD-134393; PD134393; Cefdinir; Omnicef; CFDN; Cefdinirum; Cefdinyl; CI 983; CI-983; FK 482; FK-482; Omnicef.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 33.33~79 mg/mL (84.29~199.79 mM )

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.32 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.32 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.32 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.

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Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (6.32 mM)

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 (Please use freshly prepared in vivo formulations for optimal results.)