Antifungal agent - albaconazole
Opportunistic fungal infections are a major life threatening problem to people with compromised immune systems. Systemic mycosis caused by infection with Candida albicans is a particular problem in hospital intensive care units, and infections caused by various other Candida strains, as well as Aspergillus species and a handful of other pathogens are on the rise.
Trizole drugs are undoubtedly the major players in the antifungal market, with the broad spectrum agents such as fluconazole, voraconazole and itraconazole having already proved their worth, and having much lower side-effect profiles than the likes of amphotericin B.
Further triazole derivatives are under development, and Spanish company J Uriach is working on the orally active triazole albaconazole. In two double blind randomised studies designed to test its safety, tolerability and pharmacokinetics, 48 healthy volunteers were given single doses of 80, 160, 240 of 320mg albaconazole, or multiple doses of 80 or 160mg/day for two weeks, all as an oral solution.1 It was well tolerated, with a mild headache being the most commonly reported side effect, and high plasma levels of the drug were recorded, increasing proportionally with dose.
Another safety trial looked at its interaction with the CYP3A4, which is believed to mediate its action. A total of 24 healthy male subjects were given a 80mg oral dose with 40mg simvastatin as an enzyme marker two hours later, following a single dose of simvastatin two days beforehand. Multiple doses were given for 13 days from the fifth day. No serious adverse effects were observed, and no clinically significant alterations in vital ECG parameters were experienced. In addition, pooling the results of several Phase I trials showed that it had a good cardiac safety profile.2
1. G. de la Cruz et al. Focus Fungal Infect. 13 (March 2003, Maui) 2003, Abst. 1193
2. G. de la Cruz et al. Focus Fungal Infect. 13 (March 2003, Maui) 2003, Abst. 1191