Cefodizime host-defence enhancement: considerations of dose-response relationships in healthy volunteers

Studies with cefodizime in animals have shown that this new aminothiazolyl cephalosporin, possessing a broad antibacterial spectrum, positively influences a number of immunological parameters. In most investigations in which different dosage regimens were compared, a bell-shaped dose-response relationship was determined, i.e. activity after higher doses returned to near-baseline levels. This finding is typical of most immunomodulating agents. On this basis, the results obtained in healthy subjects were reviewed. Studies for investigating the biological response modifying (BRM) properties of cefodizime have been conducted in this population with either 2 g once daily i.v. or--in the majority--with 2 x 2 g/day i.v. After seven days of treatment with 1 x 2 g daily, no relevant changes could be demonstrated in healthy subjects, whereas there was an increase in monocyte and granulocyte chemotaxis in a parallel group of patients with multiple myeloma. In contrast, treatment with 2 x 2 g daily induced higher lymphocyte responsiveness and significantly increased nonspecific phagocytosis of both neutrophils and monocytes. The experience in healthy volunteers clearly demonstrates that the latter dose, usually the highest required for antibiotic treatment with cefodizime, is still located on the upward slope of the dose-response curve of positive BRM effects.