At a minimum inhibitory concentration (MIC) of 0.05 to 1 μg/mL, cefclodine can inhibit the following pathogens: Staphylococcus aureus, penicillin-sensitive and penicillin-resistant strains, Streptococcus pyogenes, Streptococcus pneumoniae, Corynebacterium diphtheriae, Clostridium septicarum, etc. [1].

In rabbits and monkeys, cefclodine (50–500 mg/kg; intramuscular injection) shows dose-related nephrotoxicity [2].

Animal/Disease Models: Rabbits and monkeys [2]
Doses: 50, 100, 200 and 500 mg/kg
Route of Administration: intramuscularinjection
Experimental Results: 200 and 500 mg/kg caused significant changes in renal function and proximal tubule necrosis. Renal impairment does not appear to occur at doses of 50 and 100 mg/kg.

Absorption, Distribution and Excretion
Kidneys. Ceftriaxone is poorly absorbed in the gastrointestinal tract. Peak plasma concentrations are reached approximately 30 minutes after injection; 10% to 20% of plasma ceftriaxone is protein-bound. Intramuscular injections of 0.5 g and 1 g result in peak plasma concentrations of 15 μg/mL and 30 μg/mL, respectively. Approximately 75% of the administered dose is excreted in the urine, primarily through glomerular filtration. Ceftriaxone accumulates in the blood of patients with impaired renal function, and plasma concentrations are very high in patients with azotemia… Placental Drug Transport – Ceftriaxone: Appearance time in the fetus is 30 minutes; fetal/maternal concentration equilibrium time is 5 hours. /Excerpt from Table/ …/Ceftriaxone/ Easily penetrates normal eyeballs after systemic or subconjunctival administration… …Ceftriaxone… shows… very limited bone penetration after subcutaneous or oral administration in rats. Following cefadroxil administration, the average bone-to-serum concentration ratio was 1:7 within 0.25–4 hours. Biological Half-Life Cefadroxil reaches peak plasma concentration approximately 30 minutes after injection, and after its half-life (60–90 minutes), only trace amounts of drug are detectable after 8 hours. In rats, the average bone-to-serum concentration ratio of cefadroxil following oral or subcutaneous administration was 1:7 within 0.25–4 hours. Despite the concentration differences, the half-life in bone and serum was similar.

Interactions
Nonionic, anionic, and amphoteric surfactants induce a rapid, reversible hyperabsorption state of ceftriaxone in the gastric fundus of Thomas dogs… plasma concentrations… several times higher than the control group. Ceftriaxone appears to have the greatest nephrotoxic potential… unless life-threatening, it should not be used concomitantly with gentamicin/other aminoglycosides, amikacin, neomycin, paromomycin, and tobramycin, as this may increase nephrotoxicity. Ceftriaxone nephrotoxicity can be enhanced by concomitant administration of furosemide. This treatment should be avoided even in patients with mild nephropathy. …cephalosporins… may be affected by concomitant use of probenecid or sulfinpyrazone. …weakly acidic, reduced renal tubular secretion may lead to higher serum drug concentrations and longer durations of action, thereby enhancing drug activity. /Cephalexin/
Ten male rats received a single subcutaneous injection of a high-dose ceftriaxone (3750 mg/kg), methylprednisolone (100 mg/kg), or a combination of ceftriaxone and methylprednisolone, respectively. The control group received only the excipient. Urine was collected daily for 18-hour intervals during a 96-hour post-treatment collection period. Blood samples were collected at 24, 48, 72, and 96 hours post-treatment. At necropsy, the kidneys were weighed, processed, and subjected to histopathological examination. Results showed that methylprednisolone significantly reduced nephrotoxicity induced by challenge doses of cephalosporins. Rats treated with cephalosporins alone developed severe nephrotoxicity, characterized by acute tubular necrosis and elevated blood urea and creatinine levels. In contrast, most rats treated with cephalosporins in combination with methylprednisolone experienced only mild to moderate nephrotoxicity, and their blood urea and creatinine levels were lower than those treated with cephalosporins alone, indicating protected renal function. Interestingly, compared with rats treated with ceftriaxone alone, rats treated with a combination of ceftriaxone and methylprednisolone had higher levels of urinary enzymes, urinary protein, and urinary glucose. This indicates that the kidney damage and necrosis in rats treated with ceftriaxone alone were very severe, leading to a significant and rapid decrease in the number of cells capable of producing these marker enzymes; while the protective effect of methylprednisolone enabled rats treated with the combination of ceftriaxone and methylprednisolone to maintain normal output of urinary enzymes. The effects on urinary glucose and other parameters suggest an interaction between the pharmacological effects of glucocorticoids and the nephrotoxicity of ceftriaxone.

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Non-human toxicity values
Oral LD50 in mice >15 g/kg
Intramuscular LD50 in monkeys >0.2 g/kg

[1]. P. W. Muggleton, et al. Laboratory Evaluation of a New Antibiotic-Cephaloridine (Ceporin). Br Med J. 1964 Nov 14;2(5419):1234-7.
[2]. Perkins RL, et al. Cephaloridine and cephalothin: comparative studies of potential nephrotoxicity. J Lab Clin Med. 1968 Jan;71(1):75-84.

Cefaloridine is a cephalosporin compound with pyridin-1-ylmethyl and 2-thienylacetamide side groups. It is a first-generation semi-synthetic derivative of cephalosporin C and possesses antibacterial activity. It is a semi-synthetic cephalosporin derivative and also a β-lactam antibiotic allergen. Cefaloridine (or Cephalothin) is a first-generation semi-synthetic cephalosporin. It is derived from cephalosporin C and exists in a zwitterionic form under physiological pH conditions. Cefaloridine is a semi-synthetic, broad-spectrum first-generation cephalosporin with antibacterial activity. Cefaloridine binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of bacterial cell walls. Penicillin-binding proteins (PBPs) are enzymes involved in the late stage of bacterial cell wall assembly and cell wall remodeling during growth and division. PBP inactivation interferes with the cross-linking of peptidoglycan chains, which is crucial for maintaining the strength and rigidity of bacterial cell walls. This leads to weakened bacterial cell walls and ultimately cell lysis.
Cephalosporin antibiotics.

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Mechanism of action
Cephalotene and its homologues inhibit bacterial cell wall synthesis in a manner similar to penicillin. Cephalosporin drugs
Cefoglycine and ceftriaxone have acute toxicity to proximal renal tubules, partly due to their uptake by cells via contralateral anion-secreting carriers, and partly due to their intracellular attack on the transport and oxidation of anion substrates in the mitochondrial tricarboxylic acid cycle (TCA cycle). Preliminary studies of Cephalothin suggest that fatty acid (FA) metabolism plays a role in its nephrotoxicity; while studies of ceftriaxone indicate that it is a potent inhibitor of renal tubular and mitochondrial carnitine (Carn) transport.

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Therapeutic uses
Cephalosporins
Ceftriaxone's overall activity range and antibacterial spectrum are very close to Cephalothin, although some Escherichia coli strains may be more sensitive to the former. Its activity against Clostridium perfringens (Welchi II) also appears to be higher than that of Cephalothin. Occasionally, mycobacteria are sensitive to Cefaloridine…
Cefaloridine… can be administered parenterally or subconjunctivally for the treatment of intraocular infections, and also locally or subconjunctivally for the treatment of corneal ulcers.
Cefaloridine is effective against bronchitis caused by Haemophilus influenzae, but other drugs are generally more effective. This drug has also been found to be used for nebulized treatment of patients with purulent bronchitis.
For more complete data on the therapeutic uses of Cefaloridine (10 in total), please visit the HSDB record page.

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Drug Warnings
Cefaloridine can accumulate in the blood of patients with impaired renal function, and plasma concentrations are very high in patients with azotemia; a single intramuscular injection of 1 gram can result in detectable concentrations in the blood for up to 4 days. Due to its nephrotoxicity, Cefaloridine should not be given to such patients.
Although Cefaloridine is less irritating than Cephalothin, its nephrotoxicity outweighs this advantage.
In infants up to 48 hours old, ceftriaxone has a very long plasma half-life, and toxic concentrations can be reached even with significantly reduced doses.
Ceftriaxone can be administered intramuscularly or intravenously. …There is no reason to recommend this prophylactic use because other less toxic cephalosporins are available.
For more complete data on drug warnings for ceftriaxone (7 in total), please visit the HSDB records page.

C19H17N3O4S2

415.482

415.066

50-59-9

Cephaloridine hydrate;102039-86-1

5773

CRYSTALS
WHITE TO OFF-WHITE, CRYSTALLINE POWDER

184°C

0.011

1

6

5

28

687

2

O=C([O-])C=1N2C([C@@H](NC(CC3=CC=CS3)=O)[C@H]2SCC1C[N+]4=CC=CC=C4)=O

CZTQZXZIADLWOZ-CRAIPNDOSA-N

InChI=1S/C19H17N3O4S2/c23-14(9-13-5-4-8-27-13)20-15-17(24)22-16(19(25)26)12(11-28-18(15)22)10-21-6-2-1-3-7-21/h1-8,15,18H,9-11H2,(H-,20,23,25,26)/t15-,18-/m1/s1

(6R,7R)-8-oxo-3-(pyridin-1-ium-1-ylmethyl)-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Cefaloridine; Cephaloridine; Sch 11527

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)

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

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.

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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).

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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)

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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).

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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

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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.

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