Microdialysis for pharmacokinetic studies of ceftazidime in rabbit vitreous.
The method of microdialysis was used for collecting series of samples from the rabbit vitreous after systemic and intravitreous administration of ceftazidime. The purpose of the study was to compare the method with traditional pharmacokinetic sampling. Ceftazidime was injected intramuscularly (1 mg/kg) or intravitreally (1 mg) in rabbits, with a previously implanted microdialysis probe in the vitreous. The membrane was perfused with a buffer, and the dialysate was collected in samples where the concentration of the drug was analyzed by HPLC. After intramuscular administration, blood samples were taken to calculate systemic pharmacokinetics. The same procedures were repeated with rabbits with mild intraocular inflammation induced by the injection of 400 EU of endotoxin into the vitreous, 12-15 hr before drug administration. Pharmacokinetic parameters, such as half-life and AUC, were calculated. The penetration into the vitreous after intramuscular injection was higher (42%) in inflamed than in non-inflamed eyes (20%), suggesting an interference with the blood retinal barrier. Other kinetic parameters did not differ significantly between the groups. The advantage of the method is that fewer experimental animals can be used to obtain the necessary data compared to traditional pharmacokinetic methods. In conclusion, intraocular dialysis with chronically implanted probes is a technique well suited for pharmacokinetic studies of systemically administered ceftazidime or other drugs that will pass a dialysis membrane.
Waga
J
J
Department of Ophthalmology, University Hospital of Lund, Sweden.
Nilsson-Ehle
I
I
Ljungberg
B
B
Skarin
A
A
Ståhle
L
L
Ehinger
B
B
D000287:Administration, Topical; D000818:Animals; D002442:Ceftazidime / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004731:Endotoxins; D005260:Female; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D011817:Rabbits; D014822:Vitreous Body / Q000378:metabolism*
D004731:Endotoxins; D002442:Ceftazidime