The use of the African green monkey as a preclinical model for ocular pharmacokinetic studies

• Published in: Journal of ocular pharmacology and therapeutics Vol. 28; no. 3; p. 290
• Main Authors: Glogowski, Shellise, Ward, Keith W, Lawrence, Matthew S, Goody, Robin J, Proksch, Joel W
• Format: Journal Article
• Language: English
• Published: United States 01.06.2012
• Subjects: Absorption; Animals; Anterior Eye Segment - metabolism; Aqueous Humor - metabolism; Azepines - administration & dosage; Azepines - pharmacokinetics; Cercopithecus aethiops - metabolism; Drug Evaluation, Preclinical; Eye; Female; Fluoroquinolones - administration & dosage; Fluoroquinolones - pharmacokinetics; Macaca fascicularis - metabolism; Male; Models, Animal; Ophthalmic Solutions - administration & dosage; Ophthalmic Solutions - pharmacokinetics; Suspensions - administration & dosage; Suspensions - pharmacokinetics; Tears - metabolism; Tissue Distribution; Vitreous Body - metabolism
• ISSN: 1557-7732
• DOI: 10.1089/jop.2011.0164

This investigation evaluated the ocular and systemic pharmacokinetics of besifloxacin in African green monkeys compared with cynomolgus monkeys following topical ocular dosing. A suspension formulation containing 0.6% besifloxacin was administered to African green and cynomolgus monkeys. Animals were euthanized at predetermined time intervals, and ocular tissue and systemic blood samples were collected and analyzed by LC/MS/MS. In both African green and cynomolgus monkeys, high concentrations of besifloxacin were detected in anterior segment tissues, while levels in posterior segment tissues and plasma were low. Mean concentration versus time profiles of besifloxacin were generally similar between species, with rapid absorption into ocular tissues after a single dose. In anterior segment tissues, concentrations of besifloxacin were measurable throughout the 24-h sampling period in both species. Quantitatively, concentrations were consistently higher in the conjunctiva of African green monkeys compared with cynomolgus monkeys. Besifloxacin levels were also higher during the first 3 h following dosing in the tear fluid of African green monkeys, but lower in the iris/ciliary body during this timeframe. However after the 3-h time point, concentrations in the tear fluid and iris/ciliary body were similar between species. Exposure in cornea tended to be higher in African green monkeys, but the difference was less pronounced than for conjunctiva. Exposure in aqueous humor was comparable between species. In posterior segment tissues, exposure to besifloxacin tended to be higher in cynomolgus monkeys. Systemic exposure also tended to be higher in cynomolgus monkeys, but measurable levels were present in the plasma of both species throughout the 24-h sampling period. With the exception of iris/ciliary body and vitreous humor, mean ocular tissue weights were generally similar between species although a small, but statistically significant, difference was also observed in the choroid. African green monkeys may be a suitable model for preclinical ocular pharmacokinetic studies. Additional studies using a variety of compounds would be useful in determining whether the quantitative differences in ocular exposures and ocular tissue weights observed in the present investigation reflect slight variations in the procedures used in these separate experiments, or true physiological and anatomical differences between species.