Faropenem medoxomil targets bacterial penicillin-binding proteins (PBPs), which are enzymes involved in the synthesis of the bacterial cell wall peptidoglycan. By binding to PBPs, faropenem inhibits the transpeptidase activity required for cross-linking of peptidoglycan chains, leading to cell wall weakening, osmotic instability, and bacterial cell lysis. The medoxomil ester improves oral bioavailability, and the compound is hydrolyzed to active faropenem in the body.

In vitro, faropenem demonstrates broad-spectrum antibacterial activity against various Gram-positive and Gram-negative bacteria, including respiratory pathogens, urinary tract pathogens, and anaerobic bacteria. The compound's activity is assessed using standard broth microdilution or agar diffusion methods to determine minimum inhibitory concentrations (MIC). Faropenem shows stability against many β-lactamases, contributing to its activity against resistant strains.

In vivo, faropenem medoxomil is used for the treatment of respiratory tract infections, urinary tract infections, skin and soft tissue infections, and other bacterial infections. The prodrug's oral bioavailability supports convenient oral dosing. Faropenem's broad-spectrum activity and stability against β-lactamases make it a valuable option for the treatment of community-acquired infections.

Non-cellular enzyme assays for faropenem involve assessing its inhibition of penicillin-binding proteins (PBPs) using purified enzyme preparations. The enzyme is incubated with a fluorescent or radiolabeled substrate in the presence of varying concentrations of faropenem, and the inhibition of peptidoglycan synthesis is measured. IC₅₀ values for PBP inhibition are determined from dose-response curves. β-lactamase stability is assessed by incubating the compound with β-lactamase enzymes.

In vitro cellular assays for faropenem involve treating bacterial cultures with the compound and assessing growth inhibition. Cultures of Gram-positive and Gram-negative bacteria are incubated with varying concentrations of faropenem, and bacterial growth is measured by optical density or colony counting. MIC values are determined from dose-response curves. The compound's bactericidal or bacteriostatic activity is assessed using time-kill assays.

In vivo animal experiments with faropenem are conducted in animal models of bacterial infection. Mice or rats are infected with pathogenic bacteria and treated with faropenem medoxomil via oral administration. The compound's efficacy is assessed by measuring survival rates, bacterial load in tissues, and resolution of clinical signs of infection. Pharmacokinetic studies characterize absorption and distribution of the prodrug and active faropenem.

Faropenem medoxomil has a molecular weight of 413.43 and a molecular formula of C₁₇H₁₉NO₇S. It is a solid at room temperature with a purity of ≥98%. The compound is soluble in DMSO and other organic solvents. It is typically stored at -20°C, protected from light and moisture. Faropenem medoxomil is orally bioavailable, with the medoxomil ester enhancing absorption and being hydrolyzed to active faropenem.

Faropenem medoxomil is generally well-tolerated at therapeutic doses. Common side effects include gastrointestinal disturbances, headache, and skin reactions. As a β-lactam antibiotic, it may cause allergic reactions in patients with penicillin hypersensitivity. The compound should be used with caution in patients with renal impairment. Standard safety precautions should be followed.

[1].Faqi AS, Lanphear C, Gill S, Colagiovanni DB.Juvenile toxicity study of faropenem medoxomil in beagle puppies.Reprod Toxicol. 2010 Dec;30(4):619-24. Epub 2010 Aug 11.

[2].Hadley JA, Tillotson GS, Tosiello R, Echols RM.Faropenem medoxomil: a treatment option in acute bacterial rhinosinusitis.Expert Rev Anti Infect Ther. 2006 Dec;4(6):923-37.

[3].Siegert R, Berg O, Gehanno P, Leiberman A, Martinkenas JL, Nikolaidis P, Arvis P, Alefelder M, Reimnitz P.Comparison of the efficacy and safety of faropenem daloxate and cefuroxime axetil for the treatment of acute bacterial maxillary sinusitis in adults.

[4].Upchurch J, Rosemore M, Tosiello R, Kowalsky S, Echols R.Randomized double-blind study comparing 7- and 10-day regimens of faropenem medoxomil with a 10-day cefuroxime axetil regimen for treatment of acute bacterial sinusitis.Otolaryngol Head Neck Surg. 2

[5].Gettig, Jacob P.; Crank, Christopher W.; Philbrik, Alexander H. Faropenem medoxomil. Annals of Pharmacotherapy (2008), 42(1), 80-90.

Faropenem ester is an organic nitrogen and organic oxygen compound whose function is related to α-amino acids. Faropenem ester is an ester prodrug derivative of the β-lactam antibiotic faropenem. The faropenem prodrug form significantly improves oral bioavailability and allows for higher drug concentrations in vivo. Faropenem ester is a broad-spectrum antibiotic with high resistance to degradation by β-lactamases. It was jointly developed by Replidyne and Forest Laboratories. Faropenem ester is the daloxate prodrug form of faropenem, a penem antibiotic with a tetrahydrofuran substituent at the C2 position, exhibiting broad-spectrum antibacterial activity against a variety of Gram-positive and Gram-negative aerobic and anaerobic bacteria. Faropenem ester hydrolyzes in vivo, releasing active free acids. Compared to imipenem, faropenem has higher chemical stability and reduced effects on the central nervous system. Furthermore, faropenem is resistant to hydrolysis by a variety of β-lactamases. Drug Indications Faropenem has been investigated for the treatment of bacterial infections, bronchitis, otitis media, and pediatric diseases. Mechanism of Action Like other β-lactam antibiotics, faropenem exerts its effect by inhibiting bacterial cell wall synthesis. It inhibits the cross-linking between linear peptidoglycan polymer chains, the main components of the cell wall of Gram-positive bacteria. It exerts its effect by binding to and competitively inhibiting the transpeptidase (D-alanyl-alanine) used by bacteria in the synthesis of cross-linked peptidoglycan. Pharmacodynamics Faropenem has shown excellent in vitro activity against common respiratory pathogens, many aerobic Gram-positive bacteria, and anaerobes. Its activity against Gram-negative bacteria is more limited. In vivo data suggest that faropenem is effective in treating community-acquired infections, including uncomplicated skin and soft tissue infections; however, more data are needed to clarify faropenem's role in antimicrobial therapy.
Faropenem medoxomil (CAS 141702-36-5) is an orally active prodrug of the broad-spectrum penem antibiotic faropenem. It is active against Gram-positive and Gram-negative bacteria, as well as anaerobic organisms. The compound is used for the treatment of respiratory, urinary, and skin infections. Faropenem medoxomil is available from various commercial suppliers for research applications.

C17H19NO8S

397.398

397.083

C, 51.38; H, 4.82; N, 3.52; O, 32.21; S, 8.07

141702-36-5

141702-36-5;16559-89-1;

6918218

Solid powder

1.55 g/cm3

622.3ºC at 760 mmHg

4.3E-18mmHg at 25°C

1.642

0.825

1

9

6

27

775

4

O=C(N1[C@@]2(SC([C@@H]3OCCC3)=C1C(OCC4=C(OC(O4)=O)C)=O)[H])[C@@H]2[C@H](O)C

JQBKWZPHJOEQAO-DVPVEWDBSA-N

InChI=1S/C17H19NO8S/c1-7(19)11-14(20)18-12(13(27-15(11)18)9-4-3-5-23-9)16(21)24-6-10-8(2)25-17(22)26-10/h7,9,11,15,19H,3-6H2,1-2H3/t7-,9-,11+,15-/m1/s1

(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (5R,6S)-6-((R)-1-hydroxyethyl)-7-oxo-3-((R)-tetrahydrofuran-2-yl)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

A0026; A-0026; A 0026; Faropenem medoxomil; Faropenem daloxate; Faropenem medoxil.

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 : ≥ 100 mg/mL (~251.64 mM )
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.29 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 (6.29 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 (6.29 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 (6.29 mM)

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