Pharmacokinetics of newer cephalosporins after subconjunctival and intravitreal injection in rabbits
M. Barza, E. Lynch and J. L. Baum
Department of Medicine, New England Medical Center, Boston, Mass.
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 beta-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 beta-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.
