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

Abstract

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.

Therapeutic drug monitoring for triazoles

“…Nausea is more common with the suspension due to the osmotic effects of cyclodextrin; this may affect compliance and is a further indication for TDM (see Indications for therapeutic drug monitoring: general principles). The use of intravenous itraconazole enables target concentrations to be achieved within the first 48 h of therapy [30,31].…”

Antifungal drugs and rational use of antifungals in treating invasive aspergillosis: the role of the hospital pharmacist

“…Gastric acidity and food influence the bioavailability of oral formulations. It is usually used at a dose of 100-400 mg daily by oral route [11][12][13] . Its spectrum includes Candida and Aspergillus species, although no clinical data exist on its efficacy for treatment of invasive Candida infections 3 .…”

“…Its spectrum includes Candida and Aspergillus species, although no clinical data exist on its efficacy for treatment of invasive Candida infections 3 . The activity against Aspergillus isolates and some fluconazole-resistant Candida strains is its major advantage over fluconazole 11,12 .…”

Craniosynostosis due to premature closing of the sagittal suture

“…20 Itraconazole can inhibit the metabolism of drugs used in oncology practice such as warfarin, cyclosporin A, clarythromycin, tacrolimus, and busulphan, resulting in reduced clearance and prolongation of the effects of these drugs. 21 22 Itraconazole metabolism is increased by carbamazepine, phenytoin, and rifampicin.…”