Concentrations of Voriconazole in Blood and BAL-fluid After Inhalation and Oral Administration

Concentrations of voriconazole in pulmonary epithelial lining fluid and in serum are compared after inhalation of 40 mg voriconazole b.i.d. for two days or oral intake of voriconazole tablets 400 mg bid for 1 day followed by 200 mg b.i.d. for one day, respectively.

Inclusion Criteria:

• Planned bronchoscopy in relation to work-up after hemoptysis or other symptom leading to bronchoscopy
• Informed written consent
• Performance status 0-1
• Ct scan of thorax without suspicion of malignancy
• Weight t ≥ 60 og ≤ 130 kg
• Male gender or female gender in postmenopausal state defined by amenorrhea in more than 12 months.

Exclusion Criteria:

• Voriconazole treatment up to one week before inclusion
• Se-creatinin≥ 100 uM
• ALAT ≥ 70 U/l
• QT-interval > 480 ms
• Allergic reaction to voriconazole or constituents in Vfend
• Allergic reaction to other azoles
• Ischemic Heart disease, Heart failure or uncontrolled hypertension
• Treatment with statins or omeprazole, which cannot be paused for three days during voriconazole exposure
• Treatment with Efavirenz, rifabutin, ritonavir, everolimus, methadon, alfentanil, fentanyl, sufentanil, oxycodone, hydrocodone, fluconazole, aztemizol, cisaprid, pimozid, quinidine, terfenadine, carbamazepine, phenobarbital, mephobarbital, ergotamine, dihydroergotamine, rifampicine, st. johns worth, everolimus, phenytoin, warfarin, phenprocoumon, acenocoumarol, benzodiazepines as midazolam, triazolam, alprazolam, sirolimus, cyclosporine, tacrolimus, ibuprofen, diclofenac,tolbutamide, glipizide, vincristine, vinblastine or other vinca alkaloids, HIV-protease Inhibitors e.g. saquinavir, amprenavir and nelfinavir, delavirdine, nivrapine and other non-nocleaoside revers transcriptase inhibitors