Pharmacokinetics of Antifungals

Cauwenbergh, G.; Heykants, J.

doi:10.1007/978-1-4613-0655-9_23

Cited by 1 publication

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References 17 publications

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“…Although the levels of itraconazole in the cerebrospinal fluid are low, its lipophilicity results in much higher tissue and meningeal levels. In comparison, fluconazole is hydrophilic and produces high levels in the cerebrospinal fluid, but these higher levels are apparently required to obtain the same antifungal effects as itraconazole [44,[62][63][64][65]. Combining the lipophilic and the hydrophilic drugs, orally-parenterally or parenterally-orally, conferred almost no benefit [65].…”

Section: Discussionmentioning

confidence: 99%

Therapy of experimental meningeal and disseminated cryptococcosis

Cutsem

1993

Mycoses

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Summary. This study evaluated the efficacy of itraconazole, a broad‐spectrum triazole antifungal drug, which has previously been demonstrated to exhibit activity against Candida albicans C. krusei, C. glabrata, Aspergillus, Histoplasma and Blastomyces as a potential treatment for cryptococcosis. The susceptibility of 62 strains of Cryptococcus neoformans was tested in vitro. All strains were inhibited by itraconazole 0.1 μg ml‐1. Itraconazole was fungicidal after replenishment at a concentration that can easily be achieved in viva. When mice were infected intracerebrally with Cr. neoformans all control animals died, whereas only 11% and 26% of itra‐conazole‐treated animals died. In a group treated with ketoconazole, 67% died. After intravenous infection, 30% of control guinea pigs died, while other animals treated with itraconazole (5 or 10 mgkg‐1) or amphotericin B (1.25 or 2.5 mg kg‐1) all survived. Itraconazole 10 mg kg‐1 produced the best results, with brain and meningeal cultures becoming negative in 55–64% of animals. In addition, intravenously infected guinea pigs received oral or intraperitoneal treatment with itraconazole or fluconazole (each 5 or 10mgkg‐1) as monotherapy or in combination. Although both treatments were active, itraconazole 10 mg kg‐1 was the most effective. In two out of six immunosuppressed guinea pigs infected with Cr. neoformans oral itraconazole was effective, resulting in negative brain and meningeal cultures. A combination of itraconazole (5 mgkg‐1) with flucytosine or amphotericin B was more efficacious than monotherapy. Therefore, itraconazole is a potentially effective therapy for the treatment of Cyptococcus infection when administered either alone or in combination with other antifungal drugs. It may also be effective in immunocom‐promised patients. Zusammenfassung. Ziel dieser Studie war es, die Wirksamkeit von Itraconazol zu evaluieren. Hierbei handelt es sich um ein Breitband‐Antimykotikum aus der Gruppe der Triazole, dessen Aktivität gegen Candida albicans, C. krusei, C. glabrata, Aspergillus, Histoplasma und Blastomyces kürz‐lich nachgewiesen wurde und das damit als mögli‐ches Therapeutikum der Cryptococcose in Frage kommt. Es wurden 62 Stämme von Cyptococcus neofomans auf ihre Empfindlichkeit in vitro getestet, wobei alle durch 0.1 pg ml‐1 Itraconazol gehemmt wurden. Nach weiterer Zugabe wirkte Itraconazol fungizid in einer Konzentration, die sich in viva leicht erreichen läß. Wurden Mäuse intrazerebral mit Cr. neoformans infiziert, starben alle Tiere der Kontrollgruppe, während von den mit Itraconazol behandelten Tieren nur 11% und 26% starben. Bei einer Behandlung mit Ketoconzaol starben 67O/O. Nach einer intravenösen Infektion starben 30% einer Kontrollgruppe von Meerschweinchen, wogegen alle Tiere überlebten, die entweder mit Itraconazol (5 oder 10 mgkg‐1) oder Amphotericin B (1.25 oder 2.5 mgkg‐1) behandelt wurden. Die besten Ergebnisse zeigte Itraconazol in einer Konzentration von 10 mgkg‐1 im Falle von Erre‐gerkulturen aus Gehirn und Hirnhäuten: Diese wurden in...

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Section: Discussionmentioning

confidence: 99%

Therapy of experimental meningeal and disseminated cryptococcosis

Cutsem

1993

Mycoses

View full text Add to dashboard Cite

show abstract

Pharmacokinetics of Antifungals

Cited by 1 publication

References 17 publications

Therapy of experimental meningeal and disseminated cryptococcosis

Therapy of experimental meningeal and disseminated cryptococcosis

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