Microdialysis for Pharmacokinetic Studies of Ceftazidime in Rabbit Vitreous

Abstract

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.

Vitreal Pharmacokinetics of Biotinylated Ganciclovir: Role of Sodium-Dependent Multivitamin Transporter Expressed on Retina

“…Microdialysis has served as an important tool in sampling of ocular fl uids both by reducing the number of animals and providing statistically powered data. [41][42][43][44][45][46][47] The main objective of this study was to perform the ocular pharmacokinetics of GCV and its prodrug (Biotin-GCV). The pharmacokinetic studies were done to conclude whether the prodrug had better or if not comparable pharmacokinetic profi les to parent drug.…”

Issues in Pharmacokinetics and Pharmacodynamics of Anti-Infective Agents: Distribution in Tissue

“…Similar to the problem of BBB penetration, it was shown for the eye (176) that the penetration of ceftazidime into the vitreous after intramuscular injection was ϳ50% higher in inflamed than in noninflamed eyes, suggesting interference with the blood-retina barrier (177). The problem of transport across the blood-retina barrier is particularly important for the treatment of cytomegalovirus retinitis.…”

Vitreal Pharmacokinetics of Peptide-Transporter-Targeted Prodrugs of Ganciclovir in Conscious Animals

“…[18][19][20][21][22] Moreover, conscious animal model for ocular microdialysis has already been developed and validated. 17,[23][24][25][26][27] Studies from our laboratory have demonstrated the effect of probe implantation in the rabbit eye on vitreal protein levels and pharmacokinetics. 17,23 The studies have also validated the method of such probe implantation and recommended that the appropriate recovery time must be allowed before commencing any pharmacokinetic study in conscious animal model.…”