Vitreous and Aqueous Penetration of Orally and Topically Administered Moxifloxacin

Abstract

Aim: It was the aim of this study to compare the pharmacokinetics of moxifloxacin (MFLX) hydrochloride in rabbits after topical and oral administration. Methods: Three 50-µl applications of MFLX (0.5%) topical ophthalmic solution were instilled into the cul-de-sac of New Zealand white rabbits at 15-min intervals. Aqueous and vitreous samples were collected and analyzed 30–240 min after the final instillation. Assays were performed using high-performance liquid chromatography. MFLX (16 mg/kg of body weight) was administered orally. Drug concentrations in aqueous, vitreous and serum samples, collected at 30–360 min after administration, were determined using high-performance liquid chromatography. Results: After topical administration, the maximum concentrations of MFLX in the aqueous and vitreous samples were 10.2 ± 1.6 µg/ml (30 min; n = 6) and 0.10 ± 0.03 µg/ml (30 min; n = 6), respectively. After oral administration, the maximum concentrations in the aqueous, vitreous and serum samples were 0.9 ± 0.3 µg/ml (120 min; n = 6), 0.7 ± 0.2 µg/ml (240 min; n = 6) and 1.6 ± 0.9 µg/ml (120 min; n = 6), respectively. The percentages of serum MFLX concentration in the aqueous and vitreous samples after oral administration were 55.2 and 41.7%, respectively. Conclusions: The aqueous concentration of MFLX was about 10-fold higher after topical than after oral administration. However, intravitreal MFLX concentrations after oral administration were about 7-fold higher than those after topical administration. The MFLX concentrations in the aqueous humor following oral administration exceeded the minimum inhibitory concentration for 90% of the bacteria involved in ocular infection.

Bilateral acute iris transillumination following systemic administration of antibiotics

“…In addition, despite the high concentration of moxifloxacin following intravitreal administration, the rapid clearance of the drug within the first 12 h accounts for the lackof adverse reactions [17]. Conversely, oral uptake of moxifloxacin is associated with longer duration of the antibiotic within the ocular tissues explaining the adverse effects related to BAIT after systemic rather than intravitreal administration [18]. Knape et al [7] raised the hypothesis that the lens status may be a contributing factor in BAIT.…”

An ion‐paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infection

“…The mucoinert MOX–PAM NS provided increased intraocular drug absorption compared to Vigamox, including ~1.6‐fold increase in C max in the aqueous humor, and ~1.7‐fold and ~4.4‐fold higher AUC 0–24h in the aqueous humor and cornea, respectively. While the relative drug concentrations in the rat eye were informative for understanding the improved efficacy with the MOX–PAM NS, it is difficult to compare the PK parameters to prior studies in rabbits and humans that reported lower intraocular moxifloxacin concentrations after dosing Vigamox 3,33–36 . It is well known that corneal thickness varies considerably across the species, and the reported values of the average thickness of rabbit and human cornea are approximately ~2.2‐fold and 3.5‐fold higher than that of rat cornea 37,38 .…”

“…While the relative drug concentrations in the rat eye were informative for understanding the improved efficacy with the MOX–PAM NS, it is difficult to compare the PK parameters to prior studies in rabbits and humans that reported lower intraocular moxifloxacin concentrations after dosing Vigamox. 3 , 33 , 34 , 35 , 36 It is well known that corneal thickness varies considerably across the species, and the reported values of the average thickness of rabbit and human cornea are approximately ~2.2‐fold and 3.5‐fold higher than that of rat cornea. 37 , 38 Furthermore, the rats used here were albino, whereas it has been described that fluoroquinolones bind to melanin in the pigmented tissues in the eye.…”

Anisokorie mal anders

“…Pharmakologische Untersuchungen legen nahe, dass eine hohe Moxifloxacin-Konzentration im Glaskörper die Entstehung eines BAIT-Syndroms begünstigt. Diese konnte bei Kaninchen nach systemischer, nicht aber nach topischer Gabe nachgewiesen werden [5].…”