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Tissue Penetration of Cefpodoxime and Cefixime in Healthy Subjects

From the Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida (P. Liu, M. Müller, H. Derendorf); Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Vienna General Hospital, Vienna University School of Medicine, Vienna, Austria (M. Müller); Department of Pharmacology, College of Medicine, University of Florida, Gainesville, Florida (M. Grant); and Sankyo Pharma GmbH, Munich, Germany (B. Obermann).

Microdialysis is a technique that allows the measurement of free antibiotic concentrations in different tissues, which are responsible for the antibacterial activity at the infection site. In an open, randomized, 2-way crossover study in healthy volunteers, the muscle penetration of orally administered cefpodoxime (400 mg) and cefixime (400 mg) was compared using microdialysis. The results show that the total plasma concentration-time profiles of each antibiotic were similar; the area under the curve for cefpodoxime was 22.4 ± 8.7 versus 25.6 ± 8.5 mg/L•h for cefixime. However, tissue penetration was twice as high for cefpodoxime (area under the curve 15.4 ± 5.1 mg/L•h) as for cefixime (area under the curve 7.3 mg/L•h). This degree of tissue distribution is consistent with their protein binding of 21% for cefpodoxime and 65% for cefixime. After equilibration, the unbound tissue concentrations of both antibiotics were similar to their unbound plasma concentrations. Pharmacokinetic modeling was applied to describe the pharmacokinetic profiles in plasma and muscle. The study demonstrates that cefpodoxime shows greater tissue penetration than cefixime.

Key Words: Cefpodoxime • cefixime • microdialysis • tissue penetration • pharmacokinetics

Address for reprints: Hartmut Derendorf, 1600 SW Archer Road, PO Box 100494, Gainesville, FL 32610.