Biafungin (CD101), a Novel Echinocandin, Displays a Long Half-life in the Chimpanzee, Suggesting a Once-Weekly IV Dosing Option

Background: The echinocandins are an important class of antifungal agents, but are administered once
daily by intravenous (IV) infusion. An echinocandin that could be administered once weekly could
facilitate earlier hospital discharges and could expand usage to indications where daily infusions are
impractical. Biafungin is a highly stable echinocandin for once-weekly IV administration. The compound
was found to have a spectrum of activity and potency comparable to other echinocandins. In
chimpanzees single dose pharmacokinetics of IV and orally administered biafungin were compared to IV
anidulafungin, which has the longest half-life (T1/2) of the approved echinocandins.

Methods: The pharmacokinetics of biafungin and anidulafungin were compared in Pan troglodytes. Six
healthy adult female chimpanzees (three groups of two) received a single dose of either IV biafungin (1.0
mg/kg, 1 h infusion), oral biafungin (10 mg/kg, bolus gavage), or IV anidulafungin (1.0 mg/kg, 1 h
infusion). Blood draws were collected over 22 days in animals receiving biafungin and over 10 days for
anidulafungin. Quantifications of biafungin and anidulafungin were performed using qualified LC/MS/MS
and LC/MS methods, respectively. Pharmacokinetic parameters were calculated using
noncompartmental analyses.

Results: After IV administration, the T1/2 and clearance for biafungin in the chimpanzee were 81 h and
3.41 mL/h/kg, whereas for anidulafungin the observed values were 30 h and 25.2 mL/h/kg, respectively.
The oral bioavailability of biafungin was 4.5%, but exposures were high (AUC0-inf of ~137,000 ng*h/mL)
and persisted after a single dose. The apparent T1/2 after oral administration was longer than after IV
administration (99 h vs 81 h). The Tmax after oral administration occurred late (24 h).

Conclusions: Biafungin has a T1/2 nearly 3-fold longer and a clearance over 7-fold slower than those for
anidulafungin in the chimpanzee. Despite a low oral bioavailability, slow clearance leads to high AUCs
after a single oral dose. These results suggest that biafungin could potentially be administered in
patients once weekly as an IV infusion, enabling earlier hospital discharges and expansion of use to
situations where daily infusion is impractical.

Antifungal name: 

Date of article/Start date of trial: 

Friday, October 20, 2017
New antifungal drugs