Pharmacokinetics of 0.5 mg of a single and a multiple dose of intravitreal vancomycin in infected rabbit eyes.
The purpose of this study was to determine the pharmacokinetics governing distribution and elimination of 0.5 mg of intravitreal vancomycin in a single dose and in a multiple therapeutic regime in infected rabbit eyes. A total of 96 rabbits was injected with approximately 200 CFU of S. aureus intravitreally. Four days later, a single dose of 0.5 mg of vancomycin was administered to Group I (n=36). Group II (n=60) was injected with a maximum of 4 doses of 0.5 mg every 36 hr. Four animals were sacrificed at different time points in each group. Samples of vitreous, aqueous and blood were taken from each animal for analyses by HPLC. These results were evaluated using the RSTRIP program. High vancomycin concentrations were demonstrated in the vitreous of Group I, with a calculated half-life of 12 hr. In Group II, vancomycin levels were within the therapeutic range during the entire experiment. There was minimal accumulation of the drug, and the half-life did not seem to be longer with multiple doses. In conclusion, the pharmacokinetics do not change significantly when a multidose regime is used compared with a single dose. Therapeutic intravitreal concentrations of vancomycin can be achieved by using repeated doses of 0.5 mg of vancomycin.
Coco
R M
RM
Instituto de Oftalmobiología Aplicada, Ocular Pharmacology Laboratory, University of Valladolid, Spain. rosa@ioba.med.uva.es
Lopez
M I
MI
Pastor
J C
JC
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D009877:Endophthalmitis / Q000378:metabolism* / Q000382:microbiology; D015818:Eye Infections, Bacterial / Q000378:metabolism* / Q000382:microbiology; D006207:Half-Life; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics; D011817:Rabbits; D013203:Staphylococcal Infections / Q000378:metabolism* / Q000382:microbiology; D013211:Staphylococcus aureus; D014018:Tissue Distribution; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014822:Vitreous Body / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D009883:Ophthalmic Solutions; D014640:Vancomycin