Faropenem

Like other beta-lactam antibiotics, faropenem acts by inhibiting the synthesis of bacterial cell walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major component of the cell wall of Gram-positive bacteria. It does this by binding to and competitively inhibiting the transpeptidase enzyme used by bacteria to cross-link the peptide (D-alanyl-alanine) used in peptidogylcan synthesis.

Faropenem was found to be active against Enterococcus faecalis, oxacillin susceptible Staphylococci, Neisseria gonorrhoeae, Neisseria meningitides, Haemophillus influenzae, Moraxella catarrhalis, Streptococcus pyogenes, Staphylococcus saprophyticus, Staphylococcus epidermidis, Group A Streptococci, Group B Streptococci, Streptococcus milleri, Streptococcus viridans, Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, E. coli, Klebsiella spp., Proteus mirabilis, Citrobacter spp., Salmonella spp., Shigella spp., Providentia stuartii, Bacteroides fragilis, Clostridium perfringens, and Peptostreptococcus spp.

Absorption

After a single oral dose of faropenem in fasting healthy volunteers at 150, 300, and 600 mg, the plasma levels of faropenem reached C_max of 2.4, 6.2, and 7.4 mg/ml, respectively, at about 1–1.5 hours (T_max). The AUC_s of faropenem were 3.94, 11.73, and 19.59 μg.h/ml. These C_max and AUCs were proportional to the doses, and the respective urinary recoveries were 3.12%, 6.78%, and 5.26% of the dose. The half-life of faropenem is about 1 hour, irrespective of the dosage quantity.

At a single dose of 300 mg in normal healthy adults after meals, the average T_max was delayed by about 1 hour, but C_max, AUC and urinary recovery were notdifferent from those in the fasting state. In a multiple dose study with 400 mg t.i.d., the C_max on days 1, 4, and 7 (1^st, 10^th and 19^th administration) were 5.5, 4.3, and 4.8 mg/ml, respectively. The respective AUC_s were 12.5, 10.1, and 12.2 mg.h/ml, demonstrating no cumulative effect.

Distribution

Faropenem was found in the sputum of patients, fluid that oozes at the time of tooth extraction, tonsil tissues, maxillary sinus, mucous membrane tissues, female genital organ tissues, eyelids, subcutaneous cell tissues and prostate tissues.

Metabolism & Excretion

Before excretion in the urine, the absorbed faropenem gets metabolized by dehydropeptidase-I (DHP I), which is present in the kidneys. The metabolites are found in the blood and the urine. The metabolites do not demonstrate antibacterial activity. Faropenem is primarily excreted through the kidneys andthe rate of excretion in the urine (0 ~ 24 hours) of 150, 300, and 600 mg (given on an empty stomach to normal healthy adults) was 3.1 ~ 6.8%. The highest concentration in the urine was 21.7, 55.6, and 151.5 mg/ml, respectively, in 0–2 hours; after 12 hours, it was almost reduced to nil.