Measurement and pharmacokinetic analysis of unbound cephaloridine in rat blood by on‐line microdialysis and microbore liquid chromatography

Abstract

A technique involving rapid sampling of cephaloridine in rat blood was achieved using a combination of microdialysis and sensitive microbore liquid chromatography. A microdialysis probe was inserted into the jugular vein/right atrium of a Sprague-Dawley rat. Then after a real-time collection of the analyte by microdialysis, the dialysate was automatically injected into a liquid chromatographic system via an on-line injector. Following a 2 h stabilization period after the surgical procedure, cephaloridine (20 mg/kg, i.v.) was then administered via the femoral vein. Isocratic elution of cephaloridine was carried out with a mobile phase containing methanol-20 mM monosodium phosphate (25:75, v/v, pH 5.5), and the flow rate of the mobile phase was 0.05 mL/min within 10 min. Intra- and inter-assay accuracy and precision of the assay were each less than 10%. The in vivo recovery of the cephaloridine from the microdialysate was 49.7 +/- 8.0% and 42.4 +/- 8.4% for 0.5 and 1 microg/mL standards (n = 6), respectively. Based on the pharmacokinetic analysis, the elimination half-life was 32.2 +/- 8.6 min by cephaloridine administration (20 mg/kg, i.v., n = 6).

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).…”

Assaying protein unbound drugs using microdialysis techniques

“…These considerations make the jugular vein the most suitable place for blood sampling for microdialysis. In vivo blood microdialysis sampling has widely been employed to study the pharmacokinetics and metabolism of xenobiotics [34][35][36][37][38][39].…”