Abstract：
:Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85+/-0.63 microg/g wet lung weight and 0.58+/-0.30 microg/mL, with low dose group lung and plasma concentrations of 0.38+/-0.01 microg/g wet lung weight and 0.09+/-0.06 microg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.
journal_name
Int J Pharmjournal_title
International journal of pharmaceuticsauthors
Tolman JA,Nelson NA,Bosselmann S,Peters JI,Coalson JJ,Wiederhold NP,Williams RO 3rddoi
10.1016/j.ijpharm.2009.06.003subject
Has Abstractpub_date
2009-09-08 00:00:00pages
25-31issue
1eissn
0378-5173issn
1873-3476pii
S0378-5173(09)00378-0journal_volume
379pub_type
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