Simultaneous Determination of Unbound Cefoperazone in Rat Blood and Brain Using Microdialysis

Abstract

A sensitive microbore HPLC method was developed for the simultaneous determination of unbound cefoperazone in rat blood and brain using microdialysis. Two microdialysis probes were inserted into the jugular vein/right atrium and brain striatum of Sprague-Dawley rats. Cefoperazone (50 mgkg(-1), i.v.) was then administered via the femoral vein. Blood and brain dialysates were collected and eluted with a mobile phase containing methanol-100 mM monosodium phosphoric acid (30:70, v/v, pH 5.5). The wavelength of the UV detector was set at 254 nm. The detection limit of cefoperazone was 20 ng mL(-1). Isocratic separation of cefoperazone was achieved within 10 min. The intra- and inter-assay accuracy and precision of the analyses were < or =10% in the range of 0.05-10 microg mL(-1). The ratio of the area under the concentration curve of cefoperazone in rat brain and blood was estimated to be about 7-8%. It is concluded that cefoperazone is capable of penetrating the blood-brain barrier.

Effects of ampicillin, cefazolin and cefoperazone treatments on GLT-1 expressions in the mesocorticolimbic system and ethanol intake in alcohol-preferring rats

“…In addition, by selecting 100 mg/kg of daily dosing for all compounds, a qualitative comparison of efficacy between these compounds, and previously tested ceftriaxone, for GLT-1 modulatory effects was possible. Also, the CNS bioavailability of AMP, CZN, and CPZ has been studied previously, strengthening our rationale to evaluate the effects of these particular compounds on GLT-1 expression in the mesocorticolimbic pathway (Ishiyama et al, 1970, Clumeck et al, 1978a, Chang et al, 2000, Tsai and Chen, 2000). In addition to documented CNS bioavailability, AMP has the distinct advantage over ceftriaxone as an orally active antibiotic and CPZ, compared to ceftriaxone, has a unique side chain (N-methyltetrazolethiol) in its structure contributing to possible disulfiram-like actions.…”

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

“…To date, MD has been used to measure in animals the tissue PK of various antimicrobial agents, including quinolones (123,171), such as pefloxacin (171); chloramphenicol (160,161,168); ␤-lactams, such as cephalosporins, notably, cefazolin (165), cephalexin (166), cefotaxime (167), cefmetazole (162), cefuroxime (164), cephalothin (28), ceftriaxone (66,85,124,163), ceftazidime (66,169,178), cephaloridine (170), cefamandole (194), cefoperazone (29), and cefaclor (40); penicillins, notably, penicillin G (27), piperacillin and tazobactam (37,118), amoxicillin (148) (91), and stavudine (193), and of the antifungal agent fluconazole (191,192).…”

Percutaneous Microdialysis and Pharmacokinetic Study of Tongluo-Qutong Rubber Plaster in Rats by UPLC-MS/MS

“…In recent years, significant attention has been paid to in vivo performance after dermal administration of traditional Chinese medicine (TCM) preparations. 1 The active ingredients of TCM preparations for dermal use are extremely complex and present in low concentrations after transdermal absorption and distribution. Due to the limited availability of in vivo data and research, the active ingredients of these dosage forms have not been fully elucidated.…”