Tolerability, kinetics, and efficacy of subconjunctival pefloxacin in pigmented rabbits

Abstract

Pefloxacin has been shown to have good intraocular penetration when given systemically. In order to extend its clinical use, we have assessed the tolerability, kinetics, and efficacy of subconjunctival pefloxacin in phakic pigmented rabbits. The tolerability of a single subconjunctival injection of pefloxacin (0.8, 1.6, 8, or 16 mg in 0.2 ml) in the right eyes of eight rabbits was evaluated by clinical and histopathological examination. The 0.8-mg dose of pefloxacin was well tolerated. The kinetics was evaluated after a single subconjunctival injection of 0.8 mg in 18 rabbits. Animals were sacrificed at 1, 3, 5, 7, 12, or 18 h postinjection. Drug concentrations were measured by high-performance liquid chromatography. Pefloxacin was found in the cornea (maximum concentration, 18.13 micrograms/ml; half-life, 3.92 h) and in the aqueous humor (maximum concentration, 3.40 micrograms/ml; half-life, 2.14 h). Pefloxacin did not penetrate into the vitreous humor by this route. The efficacy was evaluated in an experimental model of staphylococcal corneal ulcers in eight rabbits which received two subconjunctival injections of 0.8 mg of pefloxacin at 16 and 24 h after intrastromal inoculation. The results (expressed as mean log10 CFU per milliliter +/- standard deviation) showed that pefloxacin significantly (P < 0.001) reduced the bacterial counts (4.39 +/- 0.97) compared with those in control eyes (6.46 +/- 0.69). For phakic eyes, subconjunctival pefloxacin might be of value for the treatment of corneal ulcers. Further studies are required to determine its penetration into the vitreous humor of aphakic eyes.

Effect of Eye Pigmentation on Transscleral Drug Delivery

“…2,27 The corneal AUCs in this study are comparable to the scleral AUCs on a per gram basis. The corneal levels after periocular administration could be due to a leak back along the needle tract from the site of injection, diffusion across conjunctiva into tear fluid, or the presence of a direct penetration pathway from the subconjunctival space into the aqueous FIGURE 3.…”

Assessment of Subconjunctival Delivery with Model Ionic Permeants and Magnetic Resonance Imaging

“…The low permeant concentration at the back of the eye after subconjunctival injection observed in the current study is also consistent with previous findings. For example, previous studies have reported that subconjunctival injections of aztreonam (23), ceftriaxone (24), pefloxacin (25), ciprofloxacin (26), cyclosporine (27), cefazolin, and cefamandole (28) can achieve only low concentrations of these compounds in the vitreous. In all cases, drug concentrations in the vitreous were found to be less than 0.05% of those in the injection solutions over the durations of these studies.…”

Oral Bioavailability and Plasma Disposition of Pefloxacin in Healthy Broiler Chickens

“…Pefloxacin is well distributed to the tissues [ V d(area)  = 2.36 ± L/kg and V ss  = 1.54 ± 0.33 L/kg, respectively]. The elimination half-life of pefloxacin after IV administration ( t ½β  = 8.44 ± 0.48 h) was much longer than those previously reported in other studies: 2.21 h in calves (10), 1.12–1.6 h in goats (12, 13), and 2.84–3.25 in ducks (18) but comparable to that reported in sheep ( t ½β  = 6.88 h) (16). …”

“…In poultry medicine, the potential usefulness of pefloxacin for treatment of common infections in chickens for fattening requires detailed information on pharmacokinetics properties to establish the orally administered dose necessary for maintaining bactericidal drug concentrations in the body. Although studies on the kinetic behavior of pefloxacin in many species including man ( 8 – 10 ), calves ( 11 ), rabbits ( 12 ), goats ( 13 , 14 ), pigs ( 15 ), and sheep ( 16 ) are available; pharmacokinetic investigations on pefloxacin in poultry are limited ( 17 , 18 ). Results of a preliminary study in our laboratory in chickens were presented as a poster at 9th International EAVPT Congress ( 19 ).…”