Differential Intrapulmonary Disposition of Voriconazole and Liposomal amphotericin B in Noninfected Rabbits.

A.H. GROLL, C.A. LYMAN, R. PETRAITIENE, V. PETRAITIS, A. KELAHER, A. SARAFANDI, H. CASLER, T.J. WALSH

Author address: 

University Children's Hospital, Münster, Germany, National Cancer Institute, Bethesda, MD.

Abstract: 

Background: Voriconazole (VCZ) and liposomal amphotericin B (LAMB) are effective for treatment of invasive pulmonary mycoses. Little is known, however, about their comparative disposition in the lung. Methods: Cohorts of 3 to 4 noninfected catheterized rabbits received VCZ (5 mg/kg) or LAMB as (1) single IV bolus and (2) BID or QD for 8 days. Rabbits were sacrificed at (1) 0.5 and 2 hrs after single dosing and (2) 1 h after the last dose, and plasma, epithelial lining fluid (ELF), pulmonary alveolar macrophages (PAMs) and lung tissue were obtained. Concentrations of VCZ and amphotericin B were determined as total drug by HPLC (LLQ: VCZ, 0.01µg/mL; AMB, 0.05µg/mL). Values for ELF and PAMs were calculated based on the urea dilution method and macrophage cell volume, respectively. Results: At 0.5 / 2 hrs after single dosing, mean concentrations of VCZ in ELF and lung tissue were 5.93 ±2.59 / 1.76±0.78 µg/mL and 0.115 ±0.03 / 0.107 ±0.02 µg/g. Concentrations in PAMs were
2003

abstract No: 

M-1256

Full conference title: 

43rd Interscience Conference on Antimicrobial Agents
    • ICAAC 43rd