Aerosolized Delivery of Antifungal Agents

Pulmonary infections caused by Aspergillus species are associated with significant morbidity and mortality in immunocompromised patients. Although the treatment of pulmonary fungal infections requires the use of systemic agents, aerosolized delivery is an attractive option in prevention because the drug can concentrate locally at the site of infection with minimal systemic exposure. Current clinical evidence for the use of aerosolized delivery in preventing fungal infections is limited to amphotericin B products, although itraconazole, voriconazole, and caspofungin are under investigation. Based on conflicting results from clinical trials that evaluated various amphotericin B formulations, the routine use of aerosolized delivery cannot be recommended. Further research with well-designed clinical trials is necessary to elucidate the therapeutic role and risks associated with aerosolized delivery of antifungal agents. This article provides an overview of aerosolized delivery systems, the intrapulmonary pharmacokinetic properties of aerosolized antifungal agents, and key findings from clinical studies

Comparative effects of chronic administration of the non-steroidal antiandrogens flutamide and casodex on the reproductive system of the adult male rat.

The effects of chronic blockade of androgen action by the antiandrogens flutamide and Casodex on serum and pituitary concentrations of LH and FSH, serum and testicular androgen levels, reproductive organ weights, and on spermatogenesis were compared in the adult rat. Animals were treated for 3 and 8 weeks with vehicle, Casodex (20 mg.kg-1.(day)-1, flutamide (20 mg.kg-1.(day)-1) and GnRH antagonist (150 micrograms/day, Detirelix). Treatment with GnRH antagonist suppressed gonadotropin and testosterone production, reduced the weights of testes, epididymides and seminal vesicles, and inhibited germ cell development. Flutamide administration markedly elevated serum and pituitary levels of gonadotropins as well as serum and testicular androgen concentrations. Casodex-induced elevation of gonadotropin concentrations was less pronounced and serum and testicular levels of androgens did not change significantly. The reduction of seminal vesicle weights was similar after Casodex and GnRH antagonist treatment, whereas flutamide was less effective. Testicular weight and spermatogenesis (assessed by light microscopical and flow-cytometric analysis) remained unaffected by Casodex and flutamide. It is concluded, that 1. Casodex, in contrast to flutamide, is a peripherally selective antiandrogen, and 2. Casodex influences release of gonadotropins into circulation less than flutamide. Therefore this antiandrogen might be useful clinically for selectively blocking androgen actions in the accessory sex glands