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Mechanism Of Action

Besifloxacin is a fluoroquinolone antibacterial [see CLINICAL PHARMACOLOGY, Microbiology].

Pharmacokinetics

Plasma concentrations of besifloxacin were measured in adult patients with suspected bacterial conjunctivitis who received Besivance™ (besifloxacin ophthalmic suspension) bilaterally three times a day (16 doses total). Following the first and last dose, the maximum plasma besifloxacin concentration in each patient was less than 1.3 ng/mL. The mean besifloxacin Cm, was 0.37 ng/mL on day 1 and 0.43 ng/mL on day 6. The average elimination half-life of besifloxacin in plasma following multiple dosing was estimated to be 7 hours.

Microbiology

Besifloxacin is an 8-chloro fluoroquinolone with a N-1 cydopropyl group. The compound has activity against Gram-positive and Gram-negative bacteria due to the inhibition of both bacterial DNA gyrase and topoisomerase IV. DNA gyrase is an essential enzyme required for replication, transcription and repair of bacterial DNA. Topoisomerase IV is an essential enzyme required for partitioning of the chromosomal DNA during bacterial cell division. Besifloxacin is bactericidal with minimum bactericidal concentrations (MBCs) generally within one dilution of the minimum inhibitory concentrations (MICs).

The mechanism of action of fluoroquinolones, including besifloxacin, is different from that of aminoglycoside, macrolide, and B-lactam antibiotics. Therefore, besifloxacin may be active against pathogens that are resistant to these antibiotics and these antibiotics may be active against pathogens that are resistant to besifloxacin. In vitro studies demonstrated cross-resistance between besifloxacin and some fluoroquinolones.

In vitro resistance to besifloxacin develops via multiple-step mutations and occurs at a general frequency of < 3.3 x 10^-10 for Staphylococcus aureus and < 7 x 10^-10 for Streptococcus pneumoniae.

Besifloxacin has been shown to be active against most isolates of the following bacteria both in vitro and in conjunctival infections treated in clinical trials as described in the INDICATIONS section:

CDC coryneform group G
Corynebacterium pseudodiphtheriticum*
Corynebacterium striatum*
Haemophilus influenzae
Moraxella lacunata*
Staphylococcus aureus
Staphylococcus epidermidis
Staphylococcus hominis*
Staphylococcus lugdunensis*
Streptococcus mitis group
Streptococcus oralis
Streptococcus pneumoniae
Streptococcus salivarius*

*Efficacy for this organism was studied in fewer than 10 infections.

Clinical Studies

In a randomized, double-masked, vehicle controlled, multicenter clinical trial, in which patients 1-98 years of age were dosed 3 times a day for 5 days, Besivance™ (besifloxacin ophthalmic suspension) was superior to its vehicle in patients with bacterial conjunctivitis. Clinical resolution was achieved in 45% (90/198) for the Besivance™ (besifloxacin ophthalmic suspension) treated group versus 33% (63/191) for the vehicle treated group (difference 12%, 95% CI 3% - 22%). Microbiological outcomes demonstrated a statistically significant eradication rate for causative pathogens of 91% (181/198) for the Besivance™ (besifloxacin ophthalmic suspension) treated group versus 60% (114/191) for the vehicle treated group (difference 31%, 95% CI 23% - 40%). Microbiologic eradication does not always correlate with clinical outcome in anti-infective trials.

Last reviewed on RxList: 6/11/2009
This monograph has been modified to include the generic and brand name in many instances.