Objectives: To investigate the pharmacokinetics, safety and toleration of voriconazole after a range of single and multiple oral doses. Methods: This was a single-blinded, parallel group study. 64 healthy males were randomized to voriconazole doses (mg/kg) of: 2 bid (n = 8), 4 od (n = 8), 1.5 tid (n = 11), 2 tid (n = 8), 3 bid (n = 8) and placebo (n = 21). Voriconazole was administered as single dose on days 1 and 12, and multiple dose on days 3-11. Blood samples were collected pre-dose and up to 48 h post-dose on days 1 and 12. Physical examination, ECG and routine clinical laboratory tests were performed at screening, during the study and at follow up. Results: 56 subjects completed the study. Steady-state levels were achieved after 3-5 days of multiple dosing with all regimens. Voriconazole exhibited non-linear pharmacokinetics. There was notable inter-subject variability in Cmax and AUCt and a low intra-subject variability. Voriconazole was well tolerated. The most frequent treatment-related adverse events were abnormal vision, headache and dizziness. Adverse events were mild and resolved without intervention.
Full conference title:
11th European Congress of Clinical Microbiology and Infectious Diseases
- ECCMID 11th (2001)