Background: The echinocandins are an important class of antifungal agents, but are
administered once daily by intravenous (IV) infusion. An echinocandin that offers a convenient
and more economic dosing schedule is desired.
Biafungin is a highly stable echinocandin for intermittent IV administration. The compound was
found to have a long half-life (T1/2), which may greatly reduce costs even as an IV therapy
through less frequent dosing, allowing earlier discharges for patients with negative fungal
cultures who are clinically stable. The T1/2 of biafungin in rats, dogs, and monkeys was
compared to that of anidulafungin, which has the longest T1/2 of the approved echinocandins.
Methods: The pharmacokinetics of biafungin and anidulafungin were compared in Sprague
Dawley rats, beagle dogs, and cynomolgus monkeys. In each study, single-dose (2.8 mg/kg)
pharmacokinetic (PK) parameters were evaluated over 72 h. In the rat, PK parameters were
determined in three animals each after IV bolus administration. In the dog, a crossover design
was used with four animals and administration by IV slow push. In the monkey, a crossover
design was used with three animals and administration by IV slow push. For each of these
studies, concentrations were determined by quantitative LC/MS/MS from extracted plasma and
comparison to a standard curve. Pharmacokinetic parameters were calculated using
Results: The T1/2 and clearance in the rat were 30 h and 44 mL/h/kg for biafungin and 22 h and
64 mL/h/kg for anidulafungin, respectively. Differences were more pronounced in dogs: T1/2 and
clearance were 53 h and 19 mL/h/kg for biafungin and 12 h and 47 mL/h/kg for anidulafungin,
respectively. Differences were most pronounced in monkeys: T1/2 and clearance were 40 h and
18 mL/h/kg for biafungin and 8 h and 302 mL/h/kg for anidulafungin, respectively.
Conclusions: Biafungin displays a long T1/2 and slow clearance relative to other echinocandins
in multiple species, with the differences trending more pronounced in higher species. These
findings warrant further investigation of biafungin as a potential once-weekly or less frequently
dosed agent, enabling earlier hospital discharges and expansion of echinocandin use to
indications where daily infusion is impractical.