Darflox Mechanism of Action

Pharmacology: Mechanism of Action: Ulifloxacin is transferred into bacterial cells in high concentration and shows antibacterial activity by inhibiting the activity of DNA gyrase.
In vitro Antibacterial Activity: Ulifloxacin has a broad antibacterial spectrum against gram-positive and gram-negative bacteria. Especially, it shows potent antibacterial activity against gram-negative bacteria eg, Pseudomonas aeruginosa, Serratia marcescens and Enterobacter sp, etc. Ulifloxacin has a prompt and potent bactericidal activity and the minimum inhibitory concentration (MIC) value is nearly equal to the minimal bactericidal concentration (MBC) value; even in sub-MIC, it shows bactericidal activity.
Therapeutic Effect on Experimental Infections: In mice, prulifloxacin showed an excellent protective effect in experimental systemic infections and a good therapeutic effect on experimental infections eg, respiratory and urinary tract infections, etc, caused by Pseudomonas aeruginosa, etc.
Clinical Studies: The results of clinical studies, including comparative and open studies are summarized as follows. The usefulness of prulifloxacin in the treatment of patients with respiratory tract infections (secondary infections in chronic respiratory lesion, pneumonia) and complicated urinary tract infections (pyelonephritis, cystitis) was confirmed in double-blind comparative studies. (See Table 1.)

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Microbiology: Susceptible Bacteria: Ulifloxacin-susceptible strains of Staphylococcus sp, Streptococcus sp, Streptococcus pneumoniae, Enterococcus sp, Moraxella (Branhamella) catarrhalis, Escherichia coli, Shigella sp, Salmonella sp (excluding Salmonella typhi and Salmonella paratyphi), Citrobacter sp, Klebsiella sp, Enterobacter sp, Serratia sp, Proteus sp, Vibrio cholerae, Haemophilus influenzae, Pseudomonas aeruginosa and Peptostreptococcus sp.
Pharmacokinetics: Blood Concentration: Prulifloxacin is a prodrug type of antibacterial agent that is absorbed in the upper small intestine after oral administration. It is hydrolyzed in intestinal tissue, portal vein, blood and liver, and distributed throughout the body as an active form, ulifloxacin. Table 2 shows pharmacokinetic parameters obtained after single oral administration of prulifloxacin 132.1, 264.2 or 528.4 mg (the approved single dose of prulifloxacin is 264.2-396.3 mg) to healthy adults at fasting. (See Table 2.)

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Protein Binding: Binding rates to human serum protein determined by ultrafiltration method were 50.9-52.1% in a ulifloxacin concentration range of 0.1-10 mcg/mL (in vitro).
Distribution: After oral administration of prulifloxacin 264.2 mg to patients, the maximum ulifloxacin concentrations in prostate, gallbladder, female genitalia, skin tissue, otorhinolaryngological tissue, ocular tissue and sputum were 1.21-8.25 mcg/g (mL) and the ratios to the serum concentrations were 1.79-58.2. Good transfer to body fluid and tissue was confirmed.
Metabolism and Excretion: Prulifloxacin was metabolized mainly to ulifloxacin in intestinal tissue, portal vein blood and liver. The metabolites of ulifloxacin included modified piperazinyl group and glucuronide were observed in plasma and urine. The cumulative urinary ulifloxacin excretion rates (0-24 hrs) in healthy adults administered with prulifloxacin 132.1 or 264.2 mg were 43.1% and 36.2%, respectively. No accumulation was observed after repeated administration of prulifloxacin.
Patients with Renal Function Disorder and Elderly: The pharmacokinetic parameters in patients with renal function disorder and elderly patients administered a single oral dose of prulifloxacin 264.2 mg after a meal are shown in Tables 3 and 4, respectively. As compared with healthy adults, prolonged half-life of serum ulifloxacin concentration, increased AUC and reduced cumulative urinary ulifloxacin excretion rates were observed. (See Tables 3 and 4.)

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