Tolerability and Pharmacokinetics (PK) of Co-Administered Anidulafungin (ANID) and Voriconazole (VORI)

J. A. DOWELL 1, J. SCHRANZ 1, J. WILSON 1, A. BARUCH 2, G. FOSTER 2

Author address: 

1 Vicuron Pharmaceuticals, King of Prussia, PA, 2 Pfizer Inc., New York, NY

Abstract: 

Background: There is considerable interest in combining triazole and echinocandin antifungal agents for invasive fungal infections. ANID (Vicuron Pharmaceuticals) is a novel semi-synthetic echinocandin in late-stage development for the treatment of serious fungal infections. VORI (VFEND® ; Pfizer Inc) is an extended-spectrum triazole antifungal agent with demonstrated efficacy against invasive aspergillosis and candidiasis. A drug interaction study was performed to examine PK and safety of co-administered ANID and VORI. Methods: A blinded, randomized, multiple-dose, cross-over study was conducted in healthy subjects. In a random sequence, each subject received: IV ANID with PO placebo, IV placebo with PO VORI, and IV ANID with PO VORI. ANID was given as 200 mg Day 1, then 100 mg/day (Day 2-4). VORI was given 400 mg q 12 h Day 1, then 200 mg q 12 h (Day 2-4). Study periods were separated by at least 11 days. Safety was assessed by lab tests, physical examinations, vital signs, ECGs, and adverse events (AEs). ANID and VORI PK parameters were determined at steady-state using non-compartmental methods and included maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUCSS). Results: Eighteen healthy males were enrolled in the study; 17 subjects (ages 20-40 years) completed all study periods. No dose-limiting toxicities occurred and all AEs were mild. Neither ANID nor VORI PK parameters were affected by co-administration; log-transformed PK parameter ratios were within the 80 - 125% equivalence interval. Conclusions: ANID and VORI may be co-administered together. The combination is well tolerated with no detectable PK interaction. [Table1]
2004

abstract No: 

A-462-2004

Full conference title: 

44th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 44th