Itraconazole Therapy in Lymphangitic and Cutaneous Sporotrichosis

Restrepo, Ángela

doi:10.1001/archderm.1986.01660160069021

Cited by 139 publications

(16 citation statements)

References 8 publications

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“…However, rare but severe hepatoxicity associated with itraconazole has also been reported. Up to 7% of patients receiving itraconazole have elevated ALT levels (24). Moreover, fatalities due to hepatic failure have been reported in patients receiving itraconazole (38).…”

Section: Discussionmentioning

confidence: 99%

“…Although itraconazole is known to be relatively well tolerated, about 7% of patients who received the drug experience hepatotoxicity (24). In addition to lanosterol 14 alpha-demethylase (25), itraconazole is also known to be a potent inhibitor of human liver cytochrome P450 3A4 (CYP3A4), accounting for its extensive drug-drug interactions with other medications (26).…”

Section: Introductionmentioning

confidence: 99%

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Divergence of Antiangiogenic Activity and Hepatotoxicity of Different Stereoisomers of Itraconazole

Shim

Bumpus

et al. 2016

Clinical Cancer Research

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Purpose: Itraconazole is a triazole antifungal drug that has recently been found to inhibit angiogenesis. Itraconazole is a relatively well-tolerated drug but shows hepatotoxicity in a small subset of patients. Itraconazole contains three chiral centers and the commercial itraconazole is composed of four cis-stereoisomers (named IT-A, IT-B, IT-C, and IT-D). We sought to determine whether the stereoisomers of itraconazole might differ in their antiangiogenic activity and hepatotoxicity.Experimental Design: We assessed in vitro antiangiogenic activity of itraconazole and each stereoisomer using human umbilical vein endothelial cell (HUVEC) proliferation and tube formation assays. We also determined their hepatotoxicity using primary human hepatocytes in vitro and a mouse model in vivo. Mouse Matrigel plug and tumor xenograft models were used to evaluate in vivo antiangiogenic and antitumor activities of the stereoisomers.Results: Of the four stereoisomers contained in commercial itraconazole, we found that IT-A (2S,4R,2 0 R) and IT-C (2S,4R,2 0 S) were more potent for inhibition of angiogenesis than IT-B (2R,4S,2 0 R) and IT-D (2R,4S,2 0 S). Interestingly, IT-A and IT-B were more hepatotoxic than IT-C and IT-D. In mouse models, IT-C showed more potent antiangiogenic/antitumor activity with lower hepatotoxicity compared with itraconazole and IT-A.Conclusions: These results demonstrate the segregation of influence of stereochemistry at different positions of itraconazole on its antiangiogenic activity and hepatotoxicity, with the 2 and 4 positions affecting the former and the 2 0 position affecting the latter. They also suggest that IT-C may be superior to the racemic mixture of itraconazole as an anticancer drug candidate due to its lower hepatotoxicity and improved antiangiogenic activity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Divergence of Antiangiogenic Activity and Hepatotoxicity of Different Stereoisomers of Itraconazole

Shim

Bumpus

et al. 2016

Clinical Cancer Research

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“…It is effective in the treatment of dermatomycosis, ony chomycosis and also other common fungal infections such as vaginal candidiasis [9] and pityriasis versicolor [10]. It has also been shown to be effective in systemic mycoses [11][12][13][14][15]. Because of the changing epidemiology of superfi cial skin infections, its broad spectrum of activity is partic ularly useful.…”

Section: Introductionmentioning

confidence: 99%

Clinical Experience with Short Schedules of Itraconazole in the Treatment of Tinea corporis and/or Tinea cruris

Parent

Decroix²,

Heenen³

1994

Dermatology

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Background: Superficial fungal infections have usually been considered to be caused only by dermatophytes. In recent years their epidemiology has been changing with other fungi being isolated and, thus, antifungal agents with a broad spectrum of activity, such as itraconazole, may be particularly useful. The risk/benefit ratio for any such treatment is determined by its tolerability profile and the duration of therapy. Objective: The aim was to compare the efficacy and tolerance of a shorter treatment regimen, using a higher dose of itraconazole, with a standard itraconazole regimen in the treatment of tinea corporis/cruris. Methods: An open study compared oral itraconazole 200 mg daily for 7 days with oral itraconazole 100 mg for 15 days in 153 patients with tinea corporis/cruris. Results: At follow-up all patients in both groups were clinically cured or markedly improved. However, mycological cures were greater in the 7-day treatment group (90%), and the onset of clinical and mycological cure was faster in this group. Conclusions: Itraconazole, 200 mg daily for 7 days, offers a short convenient and effective treatment option for tinea corporis and tinea cruris.

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“…Clinical responses have been reported in patients with systemic mycoses, including coccidioidomycosis, sporotrichosis, chromoblastomycosis, and aspergillosis. Usual treatment regimens have included daily dosing at 400 mg or less (2,4,8,21,23,28,29,34). Few adverse effects have been noted in the treatment of human mycoses with doses of up to 400 mg/day (2,4,8,21,23,28,29,34,36).…”

mentioning

confidence: 99%

High-dose itraconazole in the treatment of severe mycoses

Sharkey

Rinaldi

Dunn

et al. 1991

Antimicrob Agents Chemother

138

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Eight patients with systemic mycoses and with prior treatment failures were treated with itraconazole (600 mg/day) for a mean duration of 5.5 months. All six patients without AIDS experienced improvement or stabilization of their fungal infections while receiving high-dose itraconazole, although two patients later experienced treatment failures, one by relapse and one by progression, on lower doses. Treatment failures also occurred in the two patients with AIDS and cryptococcal meningitis. The failures were associated with low serum itraconazole concentrations (<2.5 ,ug/ml) in both patients. All other patients had mean trough levels in serum above 5 ,ug/ml. One patient who was improving on 600 mg/day developed a progressive infection after reduction of the dose to 400 mg/day. Side effects included reversible adrenal insufficiency in one patient; severe hypokalemia, mild diastolic hypertension, and rhabdomyolysis in one patient; mild hypokalemia and hypertension in four other patients; and breast tenderness in one patient. The mean decrease in serum potassium during treatment was statistically significant (P = 0.05). Selected patients with severe systemic mycoses may benefit from prolonged high-dose itraconazole treatment. However, 600 mg/day may be approaching the upper limits of acceptable dosing for long-term treatment.

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Itraconazole Therapy in Lymphangitic and Cutaneous Sporotrichosis

Cited by 139 publications

References 8 publications

Divergence of Antiangiogenic Activity and Hepatotoxicity of Different Stereoisomers of Itraconazole

Divergence of Antiangiogenic Activity and Hepatotoxicity of Different Stereoisomers of Itraconazole

Clinical Experience with Short Schedules of Itraconazole in the Treatment of Tinea corporis and/or Tinea cruris

High-dose itraconazole in the treatment of severe mycoses

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