[Caspofungin: mode of action and therapeutic applications].
METHODS
Since the last two decades, the incidence of invasive fungal infections has drastically increased. It becomes urgent to enlarge the panel of antifungal drugs with more potent activity and less toxicity. Since the target of all previously available antifungal agents is the synthesis of ergosterol located in the fungal membrane, the fungicidal activity of echinocandins is based on the inhibition of the glucan synthesis. Caspofungin (CAS) (Cancidas MSD France), a cyclic hexapeptide semisynthetic derivative of pneumocandin B, is the first available drug belonging to this new class.


RESULTS
CAS has a fungicidal activity covering a wide range of pathogens, including Candida spp. Data from animal and human studies demonstrate that the drug is 96% plasmatic protein bound and the proposed route of elimination is hepatic. For the treatment of systemic, oesophageal and oropharyngeal candidiasis, CAS has the same efficacy as amphotericin B or as triazoles. Among 50% of patients suffering of invasive aspergillosis with intolerance or resistance to classical treatments, CAS induces a successful response and even more in combination with these drugs. For patients with fever and neutropenia, the efficacy of CAS is non inferior than Ambisome. CAS is generally well tolerated. The most common adverse effects are fever, nausea, vomiting and complication at the infusion point of the vein. CAS has a better tolerability than amphotericin B and a similar one compared to fluconazole (FCZ) but with less drug interactions.


CONCLUSIONS
For rare but severe localisations (i.e.: endocarditis, cerebral, arthritis, etc.), CAS combinations with classical antifungal drugs could be tested in order to improve the life time in patients suffering from systemic fungal infections.
Datry
A
A
Service de parasitologie-mycologie, CHU Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France. annick.datry@psl.ap-hop-paris.fr
Bart-Delabesse
E
E
D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002177:Candidiasis / Q000188:drug therapy; D000077336:Caspofungin; D054714:Echinocandins; D006801:Humans; D055666:Lipopeptides; D009181:Mycoses / Q000188:drug therapy*; D010456:Peptides, Cyclic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015203:Reproducibility of Results
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D000077336:Caspofungin