Cefetamet pivoxil is an oral cephalosporin with enhanced affinity for the target penicillin-binding proteins 1 and 3 and an increased stability to beta-lactamases compared with older cephalosporins, such as cefalexin or cefaclor. The pharmacokinetics of cefetamet pivoxil was determined after the seventh and final dose of 500 mg of cefetamet pivoxil in eight healthy volunteers. Concentrations in plasma and cantharidin-induced skin blister fluid were determined by a high-performance liquid chromatography method. In addition, protein binding was assessed. Cmax was 4.8 +/- 1.7 micrograms/ml in skin blister fluid and 5.1 +/- 2.1 micrograms/ml in plasma. Tmax was delayed in skin blister fluid compared with plasma (3.9 +/- 1 versus 2.8 +/- 0.8 h; P < 0.001), and t1/2 was longer in skin blister fluid than in plasma (3.1 +/- 0.5 versus 2.3 +/- 0.3; P < 0.005). The mean percent penetration into cantharide blister fluid was 129% +/- 24% when measured as total drug and 149% +/- 28% when measured as free drug (P < 0.001). These data suggest that cefetamet has an excellent penetration into inflammatory interstitial fluid.