Tissue penetration of cefpodoxime into the skeletal muscle and lung in rats.
OBJECTIVE
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.
Liu
Ping
P
Department of Pharmaceutics, College of Pharmacy, University of Florida, 1600 SW Archer Road, P.O. Box 100494, Gainesville, FL 32610, USA.
Fuhrherr
Richard
R
Webb
Alistair I
AI
Obermann
Bernd
B
Derendorf
Hartmut
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D015296:Ceftizoxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005110:Extracellular Space / Q000378:metabolism; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008168:Lung / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D000097623:Cefpodoxime
D000900:Anti-Bacterial Agents; D015296:Ceftizoxime; D000097623:Cefpodoxime