AIMS: To compare the serum concentrations of itraconazole and hydroxyitraconazole after treatment with itraconazole cyclodextrin solution and itraconazole capsules in human immunodeficiency virus (HIV) positive patients with oral candidosis. METHODS: The pharmacokinetics of itraconazole and its active metabolite hydroxy-itraconazole were assessed on days 1 and 7 of therapy in acquired immunodeficiency syndrome (AIDS) patients with oral candidosis taking either itraconazole solution or capsules and the serum concentrations (measured by high performance liquid chromatography) correlated with the clinical response to therapy. In addition, the in vitro susceptibility of Candida spp isolates taken from patients at the start of the therapy was assessed. RESULTS: Nine of 16 patients treated with itraconazole capsules and eight of 15 treated with the solution responded to treatment. Three of the non-responders in each treatment group were infected with isolates resistant to itraconazole in vitro. Although with both preparations there was considerable inter-patient variability in the maximum recorded serum concentrations of itraconazole, they were significantly lower on day 1 and day 7 in those receiving capsules compared with those taking the solution. Patients unresponsive to therapy, but infected with susceptible isolates, had significantly lower concentrations of itraconazole and hydroxyitraconazole levels on days 1 and 7 than patients responding to treatment. However, patients infected with itraconazole resistant isolates (tested in vitro) failed to respond to treatment despite achieving similar serum concentrations of itraconazole and hydroxy-itraconazole to the responsive patients. For patients with in vitro susceptible isolates a serum itraconazole concentration of < 1000 ng/ml on day 7 was predictive of therapeutic failure (specificity 71%, sensitivity 100%). CONCLUSIONS: Itraconazole cyclodextrin solution achieves higher serum itraconazole and hydroxy-itraconazole concentrations than the capsule formulation in AIDS patients, and this is associated with improved efficacy.
AIMS: To compare the serum concentrations of itraconazole and hydroxyitraconazole after treatment with itraconazole cyclodextrin solution and itraconazole capsules in human immunodeficiency virus (HIV) positivepatients with oral candidosis. METHODS: The pharmacokinetics of itraconazole and its active metabolite hydroxy-itraconazole were assessed on days 1 and 7 of therapy in acquired immunodeficiency syndrome (AIDS) patients with oral candidosis taking either itraconazole solution or capsules and the serum concentrations (measured by high performance liquid chromatography) correlated with the clinical response to therapy. In addition, the in vitro susceptibility of Candida spp isolates taken from patients at the start of the therapy was assessed. RESULTS: Nine of 16 patients treated with itraconazole capsules and eight of 15 treated with the solution responded to treatment. Three of the non-responders in each treatment group were infected with isolates resistant to itraconazole in vitro. Although with both preparations there was considerable inter-patient variability in the maximum recorded serum concentrations of itraconazole, they were significantly lower on day 1 and day 7 in those receiving capsules compared with those taking the solution. Patients unresponsive to therapy, but infected with susceptible isolates, had significantly lower concentrations of itraconazole and hydroxyitraconazole levels on days 1 and 7 than patients responding to treatment. However, patients infected with itraconazole resistant isolates (tested in vitro) failed to respond to treatment despite achieving similar serum concentrations of itraconazole and hydroxy-itraconazole to the responsive patients. For patients with in vitro susceptible isolates a serum itraconazole concentration of < 1000 ng/ml on day 7 was predictive of therapeutic failure (specificity 71%, sensitivity 100%). CONCLUSIONS:Itraconazole cyclodextrin solution achieves higher serum itraconazole and hydroxy-itraconazole concentrations than the capsule formulation in AIDSpatients, and this is associated with improved efficacy.
Authors: T C Hardin; J R Graybill; R Fetchick; R Woestenborghs; M G Rinaldi; J G Kuhn Journal: Antimicrob Agents Chemother Date: 1988-09 Impact factor: 5.191
Authors: J A Barone; B L Moskovitz; J Guarnieri; A E Hassell; J L Colaizzi; R H Bierman; L Jessen Journal: Antimicrob Agents Chemother Date: 1998-07 Impact factor: 5.191
Authors: Tania K Shishido; Jouni Jokela; Clara-Theresia Kolehmainen; David P Fewer; Matti Wahlsten; Hao Wang; Leo Rouhiainen; Ermanno Rizzi; Gianluca De Bellis; Perttu Permi; Kaarina Sivonen Journal: Proc Natl Acad Sci U S A Date: 2015-10-16 Impact factor: 11.205
Authors: Andreas H Groll; Lauren Wood; Maureen Roden; Diana Mickiene; Christine C Chiou; Ellen Townley; Luqman Dad; Stephen C Piscitelli; Thomas J Walsh Journal: Antimicrob Agents Chemother Date: 2002-08 Impact factor: 5.191