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

Study Overview
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Brief Summary
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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.

Conditions
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Invasive Aspergillosis

Intervention / Treatment
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* Drug: Voriconazole


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhaled voriconazole<br>12 patients inhale voriconazole 40 mg b.i.d for two days | Drug: Voriconazole<br> <br> |
| Active Comparator: Oral Voriconazole<br>12 patients ingest voriconazole tablets 400 mg b.i.d for one day followed by 200 mg b.i.d for one day | Drug: Voriconazole<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Voriconazole concentration in serum |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Voriconazole concentration in lunge epithelial lining fluid |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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voriconazole, inhalation, aerosol, epithelial lining fluid, concentration, pharmacokinetic