Different doses of cefetamet pivoxil (Ro 15-8075) in the treatment of acute uncomplicated gonococcal urethritis in men

Abstract

In an open, dose-finding study, a 100% cure rate was observed in patients suffering from uncomplicated gonococcal urethritis who were treated with a single oral dose of either 1.2 g (n = 10), 0.8 g (n = 11), or 0.4 g (n = 10) of cefetamet pivoxil. The MICs of cefetamet for all gonococcal strains ranged from 0.001 to 0.12 ,ug/ml, and the MIC for 90% of the strains tested was 0.008 Lg/ml. Cefetamet pivoxil was ineffective against Chlamydia trachomatis in 3 of 31 patients. Side effects were minor.The incidence of plasmid-and chromosome-mediated drug resistance of Neisseria gonorrhoeae to treatment with penicillin or tetracycline has become a serious worldwide problem (1,6,9,13,14). The development of an alternative anitmicrobial therapy is therefore justified. Intramuscular treatment of patients with broad-spectrum cephalosporins has proved to be highly effective in the eradication of penicillinase-producing N. gonorrhoeae (PPNG) and nonpenicillinase-producing N. gonorrhoeae (non-PPNG) and is therefore the therapy of first choice in our clinic (8,12).Cefetamet pivoxil (Ro 15-8075) is a new oral cephalosporin. When given orally with food, approximately 50% of this prodrug ester is absorbed in the intestinal tract and is hydrolyzed into the active free acid cefetamet (2, 3). A single oral dose of 1.5 g of cefetamet pivoxil results in a maximum concentration in plasma of 7.4 + 1.3 ,ug/ml after approximately 5 h. The elimination half-life is 2.3 h. Cefetamet is eliminated predominantly via the kidneys. Thus, its elimination is influenced considerably by renal function.Cefetamet pivoxil possesses an effective in vitro activity against PPNG and non-PPNG, with MICs ranging from 0.0015 to 0.125 p.g/ml, a MIC for 50% of the strains tested of 0.007 jig/ml, and a MIC for 90% of the strains tested of 0.015 ,ug/ml (investigational drug brochure, F. Hoffmann-La Roche & Co. AG, Basel, Switzerland, 1988 evidence of a severe disease (e.g., renal insufficiency, hepatic deficiency, or syphilis), and patients who were treated with other antibiotics within the preceding 15 days were excluded from this study. Fourteen patients were treated with 1.2 g, 16 were treated with 0.8 g, and 11 were treated with 0.4 g of cefetamet pivoxil, which was given as a single oral dose.All participants were requested to return for follow-ups 2 to 3 days and 7 to 8 days after therapy and to refrain from sexual contact during the study period.