Concentrations in plasma and safety of 7 days of intravenous itraconazole followed by 2 weeks of oral itraconazole solution in patients in intensive care units.
Pharmacokinetics and safety of a hydroxy-beta-propyl solution of itraconazole were assessed in 16 patients in an intensive care unit. On the first 2 days, four 1-h infusions of 200 mg were given at 0, 8, 24, and 32 h. From day 3 to 7, inclusive, a single 1-h infusion of 200 mg of itraconazole was given daily. The intravenous (i.v.) treatment was directly followed by repeated administrations of an oral solution of itraconazole at a dosage of either 200 mg once daily or 200 mg twice daily (b.i.d.). During i.v. treatment, steady-state concentrations of itraconazole and hydroxy-itraconazole in plasma were reached within 48 and 96 h, respectively. At the end of i.v. treatment, mean (+/- standard deviation) itraconazole and hydroxy-itraconazole trough concentrations in plasma were 0.344 +/- 0.140 and 0.605 +/- 0.205 microg/ml, respectively. After the 2-week oral follow-up of 200 mg once daily the mean trough concentration had decreased to 0.245 microg/ml, whereas after 200 mg b.i.d. it increased to 0.369 microg/ml. Diarrhea during oral treatment appeared to be dose related and may be due to the solvent hydroxypropyl-beta-cyclodextrin. More severe laboratory abnormalities were noted during the i.v. than the oral treatment phase, probably related to more severe illness in that period of intensive care, but none proved clinically important. These results suggest that plasma itraconazole levels above 0.250 microg/ml may be achieved and maintained with the 1-week i.v. schedule followed by b.i.d. oral administration, whereas the once-daily oral follow-up seems to be a suboptimal treatment.
Vandewoude
K
K
Department of Intensive Care, Universitair Ziekenhuis Gent, Belgium.
Vogelaers
D
D
Decruyenaere
J
J
Jaqmin
P
P
De Beule
K
K
Van Peer
A
A
Woestenborghs
R
R
Groen
K
K
Colardyn
F
F
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000009:adverse effects* / Q000097:blood* / Q000627:therapeutic use; D003505:Cyclodextrins / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D017964:Itraconazole / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000097:blood* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control; D012996:Solutions; D047392:beta-Cyclodextrins
D000935:Antifungal Agents; D003505:Cyclodextrins; D012996:Solutions; D047392:beta-Cyclodextrins; C084794:hydroxyitraconazole; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D017964:Itraconazole