title: Interstitial tissue concentrations of cefpodoxime.
abstract: Microdialysis is a technique that allows the measurement of concentrations of free antibiotic in tissue. The free antibiotic concentration is responsible for the antibacterial effect at the target site. We used microdialysis in animal and human studies to investigate the tissue penetration of cefpodoxime. In the animal study, total plasma and free muscle and lung concentrations of cefpodoxime were measured after male Wistar rats had received either 10 mg/kg or 20 mg/kg i.v. cefpodoxime over 5 h or a continuous i.v. infusion of 260 microg/h cefpodoxime after a loading dose of 6 mg/kg. Free muscle concentrations of cefpodoxime were similar to free lung concentrations and therefore provided a surrogate measure of cefpodoxime concentrations at the pulmonary target site. In an open, randomized, two-way crossover, single-dose study in six healthy male volunteers, total plasma and free muscle concentrations were measured after a single oral dose of cefpodoxime 400 mg or cefixime 400 mg. The total plasma concentrations of each antibiotic were similar and higher than free muscle concentrations. The tissue penetration of cefpodoxime was, however, greater than that of cefixime, as shown by two-fold higher peak free muscle concentrations after dosing with cefpodoxime than with cefixime (2.1 mg/L versus 0.9 mg/L). In addition, the area under the curve for tissue (AUC(t)) of cefpodoxime (400 mg) was more than double that of cefixime (400 mg), based on free antibiotic concentrations (15.4 mg x h/L versus 7.3 mg x h/L). These findings indicate that, taking into account pharmacokinetic/pharmacodynamic considerations, cefpodoxime is likely to be more efficacious than cefixime, due to its greater tissue penetration.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
authors.forename: Maria
authors.initials: M
authors.lastname: Grant
authors.forename: Alistair I
authors.initials: AI
authors.lastname: Webb
authors.forename: Bernd
authors.initials: B
authors.lastname: Obermann
authors.forename: Hartmut
authors.initials: H
authors.lastname: Derendorf
mesh_terms: 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*; D018592:Cross-Over Studies; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008168:Lung / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009132:Muscles / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014018:Tissue Distribution; D000097623:Cefpodoxime
chemical_list: D000900:Anti-Bacterial Agents; D015296:Ceftizoxime; D000097623:Cefpodoxime