Tissue penetration of cefpodoxime into the skeletal muscle and lung in rats
Ping Liu1, Richard Fuhrherr, Alistair I Webb
1Department of Pharmaceutics, College of Pharmacy, University of Florida, 1600 SW Archer Road, P.O. Box 100494, Gainesville, FL 32610, USA.
Purpose:
The aim of this study was to investigate the pharmacokinetics of cefpodoxime in interstitial tissue fluids (skeletal muscle and lung) in rats by microdialysis, and to examine the relationship between free drug levels in plasma and in tissues.
Methods:
Cefpodoxime was administered to anesthetized male Wistar rats as single intravenous bolus of 10 or 20 mg/kg and constant infusion of 260 microg/h with a loading dose. The protein binding of cefpodoxime in rat plasma was determined using ultrafiltration.
Results:
The average protein binding of cefpodoxime in rat plasma was 38%. The half-lives in plasma, muscle and lung were similar (approximately 5 h). After constant rate infusion, the free concentrations in the muscle and the lung were almost identical, but lower than total and free plasma concentrations. The data were modeled simultaneously using a two-compartmental body model.
Conclusions:
Free interstitial levels of cefpodoxime in muscle and lung tissue are very similar. Since muscle is more accessible than lung, free muscle concentrations may serve as a good surrogate for unbound concentrations in lung.
