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Pharmacokinetics of Newer Cephalosporins After Subconjunctival and Intravitreal Injection in Rabbits
Michael Barza, MD;
Elizabeth Lynch, MS;
Jules L. Baum, MD
Arch Ophthalmol. 1993;111(1):121-125.
Abstract
• Pharmacologic considerations suggest that third-generation cephalosporins might penetrate the vitreous humor better after periocular injection and might be eliminated less readily after intravitreous injection than older agents. We studied the sodium salts of ceftizoxime, ceftriaxone, and ceftazidime, and of an investigational cephalosporin, cefepime, in rabbits. After a single subconjunctival injection in animals with normal eyes, vitreous levels ranged from 3 to 13 mg/L. After five subconjunctival injections in rabbits with infected eyes, vitreous concentrations ranged from 12 to 34 mg/L. These concentrations are not appreciably greater than those found with older β-lactams. The vitreous half-life of the four drugs after intravitreous injection varied from 5.7 to 20 hours in rabbits with uninflamed eyes and from 9.4 to 21.5 hours in rabbits with infected eyes. Except for ceftizoxime, the half-lives were substantially longer than those for older β-lactams and suggest predominantly anterior route elimination. Vitreous penetration of these new agents after subconjunctival injection does not appear to be sufficient to overcome the need for intravitreous injections in the treatment of endophthalmitis. However, the longer vitreous half-lives of some of the newer agents may be useful if the drugs are to be given intravitreally.
Author Affiliations
From the Department of Medicine, Division of Geographic Medicine and Infectious Disease, New England Medical Center, Boston, Mass (Dr Barza and Ms Lynch), and Tufts University School of Medicine (Dr Baum), Boston. The authors have no commercial or proprietary interest in the products named or the manufacturing companies listed. Dr Barza has received honoraria for lectures from Roche Laboratories, Nutley, NJ, and Glaxo, Research Triangle Park, NC.
Footnotes
Accepted for publication September 10, 1992.
Reprints not available.
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