Pharmacokinetics of oral voriconazole in adults with cystic fibrosis

Ian Clifton, Paul Whitaker, Rachel Metcalfe, Maria Phillips, Nicola Shaw, Daniel Peckham.

Author address: 

Regional Adult Cystic Fibrosis Unit, St James' University Hospital, Leeds, West Yorkshire, United Kingdom

Abstract: 

There is increasing concern about the role of fungal diseases in people with cystic fibrosis (CF). There are reports of the use of voricaonzole in the treatment of invasive aspergillosis and allergic bronchopulmonary aspergillosis in people with CF. Previous studies have demontrated that oral itraconazole is poorly absorbed and therefore this study was designed to examine the pharmacokinetics of oral voriconazole. Nine adults with CF were administered oral voriconazole 400mg twice daily for 1 day, followed by 200mg twice daily for a further 13 days. Blood samples were taken for voricaonzole levels on day 1 and 14 at time 0, 1, 2, 4, 8, and 12 hours post the morning dose. Voriconazole levels were determined using liquid tandem mass spectrometry. From the experiemental data pharmacokinetic parameters were determined. Table 1 shows the pharmacokinetic parameters. Of note two pateints had to withdraw from the study due to side-effects, both of these patients had high drug levels. One patient suffered visual hallucination with a level of 5.5 mg/L and another patient developed deranged liver function tests with a level of 5.4 mg/L. This study demonstrates that oral voriconazole is absorbed in people with CF and therefore may potentially have a role in the treatment of fungal disease in this group of patients. The levels achieved were above the proposed breakpoint for voriconazole and aspergillus of 1.0 mg/L. we would propose that drug level monitoring would be useful particularly in the context of side-effects or lack of efficacy
2010

abstract No: 

E3499

Full conference title: 

20th European Respiratory Society conference
    • ERS 20th (2010)