Pharmacology: Antibacterial Activity: Ofloxacin shows a broad spectrum of antibacterial activity against gram-positive and gram-negative bacteria. It is active against bacteria isolated from otitis media and otitis externa, including Staphylococcus, Streptococcus and Proteus spp, Pseudomonas aeruginosa and Haemophilus influenzae.
Mechanism of Action: Ofloxacin is considered to specifically act on bacterial DNA gyrase and thus, inhibit DNA replication. Its antibacterial activity is bactericidal and causes bacteriolysis at MIC.
Pharmacokinetics: Blood Concentration: When 0.3% ofloxacin solution was instilled and allowed to maintain in the middle ear cavity at 10 drops/administration twice a day for 7 days (total of 14 times) in adult patients, the serum concentration in 30 min after administration ranged from 0.009-0.012 mcg/mL, showing a low value. Furthermore, when a single administration of ofloxacin solution at 5 drops/administration was instilled and allowed to maintain in the cavity of the middle ear in children, the serum concentration in 120 min after administration was ≤0.013 mcg/mL, similarly showing a low value.
Co-administration of the oral administration of ofloxacin with nonsteroidal anti-inflammatory drugs of phenylacetic/propionic acid derivatives may possibly cause convulsions. However, when Tarivid Otic solution was topically instilled and allowed to maintain in the ear, the peak blood concentration was 1/100 compared to oral administration. Therefore, there is practically no possibility that concomitant use with these anti-inflammatory analgesics may induce convulsion.
Oral administration of ofloxacin is contraindicated in children since the safety in children has not been established, and animal studies have shown that ofloxacin may produce arthropathy in juvenile animals. However, when Tarivid Otic solution was topically instilled and allowed to maintain in the ear, the peak blood concentration was 1/100 compared to oral administration. Safety has been confirmed in the clinical trials in children, and it is possible to use this drug for children.
Distribution: When 0.3% ofloxacin solution was instilled and allowed to maintain in the middle ear cavity at 10 drops/administration twice a day for 10 days (total of 19 times) in adult patients, the concentration in the mucosa of the middle ear in 90 min after administration was 19.5 mcg/g, and when a single administration of 0.1% ofloxacin solution at 10 drops was instilled, the concentration in the otorrhea in 30 min after administration ranged from 107-610 mcg/mL, showing a high value.
Metabolism: Reference Information (animal study).
After a single dose of 0.3% 14C-ofloxacin solution was administered into the middle ear cavity in guinea pigs, and its metabolism was investigated for up to 24 hrs. The majority of the drug was excreted (87%) in urine and 3 metabolites, which were presumed to be the demethylated form, N-oxide and glucuronide form were observed.
Excretion: Reference information (animal study).
After a single dose of 14C-ofloxacin solution was administered into the middle ear cavity in guinea pigs, and the urinary and fecal excretion of radioactivity was investigated. About 90% of the administered dose was excreted in the urine within 72 hrs after administration and a little in the feces.
Clinical Studies: The results of Japanese open-labeled clinical and double-blind studies in which ofloxacin otic solution was administered in twice daily regimen are summarized in the following tables.
Otitis Media: See Table 1.
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Moreover, its efficacy has been confirmed in double-blind comparative study in patients with otitis media using oral cefalexin as a basal medication and a placebo as a control.
Otitis Externa: See Table 2.
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Bacterial Eradication: In the open-labeled clinical study in otitis media and otitis externa, bactericidal efficacy rate by instillation of Tarivid Otic Solution once or twice a day were 97.8% (89/91 strains) for Staphylococcus aureus and 92.6% (63/68 strains) for coagulase-negative Staphylococci. All 18 strains of Streptococcus sp, including Streptococcus pyogenes (3 strains) and Streptococcus pneumoniae (4 strains), were eradicated. Proteus vulgaris (2 strains) was completely eradicated. The eradication rate was 83.3% (5/6 strains) for Proteus mirabilis, while 32 strains of Pseudomonas and 6 strains of Haemophilus influenzae were all eradicated.