Antimicrobial pharmacokinetics in endophthalmitis treatment: studies of ceftazidime.
Ceftazidime has pharmacokinetic advantages for treatment of endophthalmitis caused by gram negative-organisms by intravenous administration. Additionally, its spectrum of coverage for these organisms and its relatively low toxicity after intraocular injection are favorable attributes. These studies demonstrate that inflammation leads to a significant reduction of the blood-ocular barriers to ceftazidime. This increased permeability shortens the half-life of the drug after intraocular injection but allows a significant penetration into the eye after a single intravenous dose so that therapeutic levels are achieved. Ceftazidime appears to be removed by both the anterior and the posterior route without active transport. The experiments demonstrate the importance of the vitreous as a barrier to achieving significant concentration of antibiotic within the eye after intravenous administration and confirm the importance of the vitreous in prolonging the half-life of drugs injected intravitreally. Finally the results emphasize that the pharmacokinetic behavior of drugs for treatment of endophthalmitis must be assessed in inflamed eyes both with and without intact vitreous, since these factors play a large role in drug availability and concentration in the vitreous cavity and are the major variables in the clinical setting.
Meredith
T A
TA
Anheuser-Busch Eye Institute, St Louis University, Missouri.
D000818:Animals; D002442:Ceftazidime / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009877:Endophthalmitis / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D015818:Eye Infections, Bacterial / Q000188:drug therapy / Q000378:metabolism*; D006090:Gram-Negative Bacteria; D006207:Half-Life; D007275:Injections, Intravenous; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D014821:Vitrectomy
D002442:Ceftazidime