β-lactam

Absorption, Distribution and Excretion
Cefalotin enters the aqueous humor after subconjunctival injection, reaching peak concentration approximately 1-2 hours post-administration. Within 5 hours of administration, the ratio of aqueous humor to serum antibiotic concentration ranges from 4.0 to 67.0, indicating a biphasic process of antibiotic excretion from the aqueous humor. Studies have shown that… after subcutaneous or oral administration in rats, Cefalotin penetration into bone is very limited. The average concentration ratio of Cefalotin in bone and serum is 1:4… Despite concentration differences, the half-life in bone and serum is similar. Recently discovered drugs that actively cross the human placenta include… Cefalotin… Following administration of 1 gram of Cefalotin, the urinary concentration ranges from 0.7 to 5 mg/mL. Excretion is delayed in cases of decreased renal function… For more complete data on the absorption, distribution, and excretion of Cefalotin (11 species), please visit the HSDB records page.

---

Metabolism/Metabolites
Cefothiophene is metabolized into less active deacetylated metabolites, but 50-75% of the drug is excreted unchanged in the urine.
Approximately 25% of the administered dose is excreted in the urine as deacetylated Cefalotin.
Cefothiophene…is deacetylated in the body, and these metabolites have lower antibacterial activity than the parent compound…Deacetylated metabolites are also excreted by the kidneys.

---

Biological Half-Life
30 minutes
Injection half-life = 0.6 hours (Data from table)

Protein Binding
65-80% Interactions Concomitant use with probenecid may prolong the serum half-life of Cefalotin. Animal studies have shown that furosemide enhances the nephrotoxicity of Cefalotin. Cephalosporins may be affected by concomitant use with sulfinpyrazone. Reduced renal tubular secretion of weak acids may lead to higher serum concentrations and longer durations of action, thereby enhancing drug activity. Cephalosporins Nonionic, anionic, and amphoteric surfactants induce a rapid and reversible state of hyperabsorption in the gastric fundus of Thomas dogs…Cefalotin… For more complete data on interactions of Cefalotin (10 in total), please visit the HSDB record page.

---

Non-human toxicity values
Rats oral LD50 >10,000 mg/kg/sodium salt/
Rats intraperitoneal LD50 7716 mg/kg/sodium salt/
Mice oral LD50 >20,000 mg/kg/sodium salt/
Mice intraperitoneal LD50 5670 mg/kg/sodium salt/

[1]. Structure-based optimization of cephalothin-analogue boronic acids as beta-lactamase inhibitors. Bioorg Med Chem. 2008 Feb 1;16(3):1195-205. Epub 2007 Nov 7.

Cefalotin is a semi-synthetic first-generation cephalosporin antibiotic with an acetoxymethyl group at position 3 and a (2-thiopheneacetyl)nitrile group at positions 7 of its core structure. It is administered parenterally for use during surgery and to treat various bloodstream infections. It possesses antibacterial and antimicrobial activity. Cefalotin is a semi-synthetic derivative belonging to the β-lactam antibiotic class, allergen, cephalosporin, carboxylic acid, thiophene compound, and azabicyclic olefin. It is the conjugate acid of Cefalotin (1-). Cefalotin is a cephalosporin antibiotic. There are reports of Cefalotin's presence in bovine (Bos taurus) with relevant data. Cefalotin is a semi-synthetic, β-lactam, first-generation cephalosporin antibiotic with bactericidal activity. Cefalotin binds to and inactivates penicillin-binding protein (PBP) located on the inner membrane of the bacterial cell wall. PBP is involved in the final stages of bacterial cell wall assembly and cell wall remodeling during cell division. Inactivation of PBPs interferes with the cross-linking of peptidoglycan chains, which is crucial for maintaining the strength and rigidity of bacterial cell walls. This leads to weakening of the bacterial cell wall, ultimately resulting in cell lysis.
Cephalosporin antibiotics.

---

Indications
For the prevention of infections during surgery and the treatment of various blood, bone or joint, respiratory, skin, and urinary tract infections.

---

Mechanism of Action
The bactericidal activity of Cefalotin derives from its affinity for penicillin-binding proteins (PBPs), thereby inhibiting cell wall synthesis. Penicillin-binding proteins (PBPs) are transpeptidases that play a vital role in peptidoglycan biosynthesis. Therefore, inhibiting PBPs prevents the normal synthesis of this important cell wall component.
Cephalosporins have bactericidal activity; their mechanism of action depends on their ability to reach and bind to penicillin-binding proteins located on the bacterial cytoplasmic membrane. Cephalosporins inhibit the synthesis of bacterial septa and cell walls, likely through the action of membrane-bound transpeptidases. This prevents the cross-linking of peptidoglycan chains, which is crucial for the strength and rigidity of bacterial cell walls. Furthermore, cell division and growth are inhibited, and susceptible bacteria frequently elongate and lyse. Rapidly dividing bacteria are most sensitive to cephalosporins. /Cephalosporins/

---

Therapeutic Uses
Because Cefalotin is the least susceptible to degradation by staphylococcal β-lactamases, it is highly effective against severe staphylococcal infections (such as endocarditis).
MeSH Title: Antimicrobial Agents
Should be limited to treating severe infections caused by susceptible bacteria, most commonly in patients allergic to penicillin. /Sodium/
...Cephalosporins are...the first-line drugs for treating Klebsiella infections...They can be used as an alternative to penicillin. /Cephalosporins/
For more complete data on the therapeutic uses of Cefalotin (28 in total), please visit the HSDB record page.

---

Drug Warnings
Drug excretion is delayed in cases of decreased renal function; in cases of severe renal failure, the dosing interval must be extended.
Cefothiophene should not be used to treat bacterial meningitis.
Enterococcal infections are generally unaffected by these compounds…Cefosporins cannot cure enterococcal endocarditis, even when used concomitantly with gentamicin or streptomycin. /Cefosporins/
Patients with a history of mild or prolonged responses to penicillin appear to have a lower risk of developing a rash or other allergic reactions after cephalosporin treatment…Cefosporins should be used with caution or avoided in patients with a recent severe immediate-type reaction to penicillin. /Cefosporins/
For more complete data on drug warnings for cephalothiophene (21 in total), please visit the HSDB records page.

---

Pharmacodynamics
Cefothiophene (INN) or cephalothiophene (USAN) is a semi-synthetic first-generation cephalosporin with broad-spectrum antibacterial activity, administered via the parenteral route.

C16H16N2O6S2

396.44

396.044

C, 48.47; H, 4.07; N, 7.07; O, 24.21; S, 16.18

153-61-7

Cephalothin sodium;58-71-9

6024

White to off-white solid powder

1.6±0.1 g/cm3

757.2±60.0 °C at 760 mmHg

160-161ºC

411.8±32.9 °C

0.0±2.7 mmHg at 25°C

1.676

1.45

2

8

7

26

680

2

S1C([H])([H])C(C([H])([H])OC(C([H])([H])[H])=O)=C(C(=O)O[H])N2C([C@]([H])([C@@]12[H])N([H])C(C([H])([H])C1=C([H])C([H])=C([H])S1)=O)=O

XIURVHNZVLADCM-IUODEOHRSA-N

InChI=1S/C16H16N2O6S2/c1-8(19)24-6-9-7-26-15-12(14(21)18(15)13(9)16(22)23)17-11(20)5-10-3-2-4-25-10/h2-4,12,15H,5-7H2,1H3,(H,17,20)(H,22,23)/t12-,15-/m1/s1

(6R,7R)-3-(acetyloxymethyl)-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Cefalotin; Cephalothin; Cephalotin; Cefalothin; Cefalotina; Monosodium Salt, Cephalothin; Normon Brand of Cephalothin Sodium; Salt, Cephalothin Monosodium; Seffin; Sodium Cephalothin; Spaly Brand of Cephalothin Sodium;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

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

DMSO : 79~100 mg/mL ( 199.27~252.24 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.31 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 (6.31 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.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (6.31 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 (6.31 mM)

---

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