Cefuroxime 1-acetoxyethyl ester
[CAS# 64544-07-6]

Identification

• Classification: API >> Antibiotics >> Cephalosporin
• Name: Cefuroxime 1-acetoxyethyl ester
• Synonyms: (6R-(6alpha,7beta(Z)))-3-(((Aminocarbonyl)oxy)methyl)-7-((2-furanyl(methoxyimino)a cetyl)-amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 1-(acetyloxy)ethyl ester
• Molecular Formula: C₂₀H₂₂N₄O₁₀S
• Molecular Weight: 510.47
• CAS Registry Number: 64544-07-6
• EC Number: 638-760-6
• SMILES: CC(OC(=O)C)OC(=O)C1=C(CS[C@H]2N1C(=O)[C@H]2NC(=O)/C(=NOC)/C3=CC=CO3)COC(=O)N

Properties

• Density: 1.6±0.1 g/cm³ Calc.^*
• Index of refraction: 1.665 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS08 Danger
• Risk Statements: H317-H334
• Safety Statements: P233-P260-P261-P271-P272-P280-P284-P302+P352-P304+P340-P321-P333+P317-P342+P316-P362+P364-P403-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin sensitization	Skin Sens.	1	H317
Respiratory sensitization	Resp. Sens.	1	H334

Discovery and Applications

Cefuroxime 1-acetoxyethyl ester is a chemically modified prodrug derivative of cefuroxime, a second-generation cephalosporin antibiotic. The compound is designed to improve the oral bioavailability and pharmacokinetic properties of cefuroxime, which itself has limited absorption when administered orally due to its polar nature and low lipid solubility. The molecular structure of cefuroxime 1-acetoxyethyl ester features the core cephem nucleus of cefuroxime with an ester group formed by the attachment of a 1-acetoxyethyl moiety to the carboxyl group of cefuroxime.

This esterification masks the polar carboxylic acid group, increasing the lipophilicity of the molecule and enhancing its ability to permeate biological membranes such as the intestinal epithelium. Once absorbed, enzymatic hydrolysis of the ester bond by plasma and tissue esterases releases the active parent drug, cefuroxime, enabling it to exert its antibacterial effects.

Cefuroxime 1-acetoxyethyl ester retains the β-lactam ring fused to the dihydrothiazine ring that is characteristic of cephalosporins, crucial for its mechanism of action. Like cefuroxime, the active released antibiotic inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to cell lysis and death. This results in bactericidal activity against a broad spectrum of gram-positive and gram-negative bacteria, including *Staphylococcus aureus*, *Streptococcus pneumoniae*, *Haemophilus influenzae*, and *Escherichia coli*.

The prodrug approach with cefuroxime 1-acetoxyethyl ester addresses the limitations of cefuroxime's oral absorption, enabling effective oral therapy with improved bioavailability compared to cefuroxime axetil, another oral ester prodrug form. This improved absorption profile allows for more consistent therapeutic plasma concentrations and enhances patient compliance by facilitating oral administration.

Pharmacokinetic studies indicate that following oral administration, cefuroxime 1-acetoxyethyl ester is rapidly hydrolyzed to cefuroxime, achieving peak plasma concentrations within a timeframe suitable for effective antimicrobial therapy. The compound is subsequently excreted primarily by the kidneys in unchanged form, and dosage adjustments may be necessary in patients with impaired renal function.

The synthesis of cefuroxime 1-acetoxyethyl ester involves the esterification of the free carboxyl group of cefuroxime with 1-acetoxyethyl chloride or similar reagents under controlled conditions to yield the esterified prodrug. This chemical modification does not alter the β-lactam ring or the antimicrobial pharmacophore but significantly affects pharmacokinetic behavior.

Clinically, cefuroxime 1-acetoxyethyl ester is used in the treatment of respiratory tract infections, urinary tract infections, skin infections, and other bacterial diseases susceptible to cephalosporin antibiotics. Its improved oral absorption compared to cefuroxime sodium expands therapeutic options and dosing convenience.

Adverse effects of cefuroxime 1-acetoxyethyl ester are similar to those of other cephalosporins and may include gastrointestinal disturbances, hypersensitivity reactions, and, rarely, hematologic abnormalities. Monitoring for allergic reactions is essential, especially in patients with known β-lactam allergies.

In summary, cefuroxime 1-acetoxyethyl ester is an orally bioavailable prodrug of cefuroxime designed to enhance absorption and clinical efficacy. Through esterification, it improves pharmacokinetic properties while retaining the broad-spectrum bactericidal activity of the parent cephalosporin, making it a valuable agent in antibacterial therapy.

References

1984. Pharmacology of Cefuroxime as the 1-acetoxyethyl ester in volunteers. Antimicrobial Agents and Chemotherapy, 25(1).
DOI: 10.1128/aac.25.1.78

2021. Combination antibiotic therapy versus monotherapy in the treatment of acute exacerbations of chronic obstructive pulmonary disease: an open-label randomized trial. BMC Infectious Diseases, 21(1).
DOI: 10.1186/s12879-021-06687-3

2023. Pharmacokinetics and Target Attainment of β-lactam Antibiotics in Older People: A Systematic Review of Current Literature. Clinical Pharmacokinetics, 62(1).
DOI: 10.1007/s40262-022-01196-1