Pharmacokinetics of intravitreal carbenicillin, cefazolin, and gentamicin in rhesus monkeys

Abstract

Although intravitreal injection of antibiotics is being used more widely in treatment of bacterial endophthalmitis, the pharmacokinetic principles that underlie such therapy have been derived exclusively from experiments in the rabbit. Therefore, we studied several representative antibiotics in normal eyes of rhesus monkeys. Carbenicillin (1,000 micrograms), cefazolin (1,000 micrograms), or gentamicin (100 micrograms) was injected intravitreally. Vitreous and aqueous humors were aspirated at intervals up to 96 hours after injection. The half-life values in the vitreous humor were: carbenicillin 10 hours, cefazolin 7 hours, and gentamicin 33 hours. Concomitant intraperitoneal administration of probenecid prolonged the vitreal half-life of carbenicillin to 20 hours and of cefazolin to 30 hours. The estimated vitreous volumes in these monkeys were approximately 3.0-4.0 ml. These results are consistent with the hypothesis that, in primates as in rabbits, beta-lactam antibiotics are eliminated via the retinal route and the aminoglycoside via the anterior route. This supports the applicability of the rabbit model to the treatment of endophthalmitis in humans.