Erratum to A Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Potential in Superficial and Systemic Mycoses

Grant, Susan; Clissold, Stephen P.

doi:10.1007/bf03259618

Cited by 224 publications

(350 citation statements)

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“…This is in agreement with the observations of other investigators (16,28,32,37,38). Since protein binding is reported to be low for Flu (1,14,17), the effect of serum on its antifungal activity was not tested.…”

Section: Discussionsupporting

confidence: 92%

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Effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans

Etten

Rhee

Kampen

et al. 1991

Antimicrob Agents Chemother

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The effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans were studied. With respect to the extracellular growth of C. albicans, antifungal activity was measured in terms of MICs and minimal fungicidal concentrations as well as by determination of the concentration that effectively killed (>99.9%) C. albicans in the absence or presence (amphotericin B only) of serum. Amphotericin B was highly active in terms of killing, even at an increased inoculum size. In the presence of serum, amphotericin B activity was substantially reduced. For fluconazole, activity was restricted to inhibition of fungal growth, even after the inoculum size was reduced. With respect to the intracellular growth of C. albicans, antifungal activity was measured by using monolayers of murine peritoneal macrophages infected with C. albicans and was measured in terms of inhibition of germ tube formation as well'as effective killing (>99%) of C. albicans. Amphotericin B was highly active against C. albicans. At an increased ratio of infection, amphotericin B activity was slightly reduced. Fluconazole had no antifungal activity. Neither a reduction in the ratio of infection nor exposure of C. albicans to fluconaz'ole prior to macrophage ingestion resulted in activity against intracellular C. albicans by fluconazole. Previous exposure of C. albicans to amphotericin B resulted in increased intracellular activity of amphotericin B. The. intracellular antifungal activity of the combination of fluconazole with amphotericin B was les than that of amphotericin B alone. Amphotericin B showed fungicidal activity against C. albicans growing both extracellularly and intracellularly, whereas fluconazole inhibited growth only of extracellular C. albicans. A slight antagonistic effect between fluconazole and aiflphotericin B was found with respect to intracellular as well as extracellular C. albicans.Deep-seated candidal infections are an important cause of morbidity and mortality in immunocompromised patients (15,21,22). The current drug of choice for most systemic mycoses is still amphotericin B (AmB), but its use is restricted by a variety of toxic side effects (6,13,15,21,22). Consequently, there is a need for effective and less toxic drugs for the treatment of patients with these infections. One of these antifungal agents is the triazole fluconazole (Flu) (4,10,14,33,34,41). In vivo experimental studies suggested that Flu is active against disseminated candidiasis (8,9,29,31,32,35,37). Recently, the antifungal efficacy of Flu was demonstrated in persistently granulocytopenic rabbits when it was used for prevention or early treatment (39,40). Little is still known, however, on the role of Flu in the treatment of systemic candidiasis in immunocompromised patients. Since the host defense mechanisms in these patients are severely impaired, the intrinsic antifungal activity of the antifungal agent is of great importance for effective treatment. Unfortunately, standardized in vitro methods for assessment of ...

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Section: Discussionsupporting

confidence: 92%

“…Consequently, there is a need for effective and less toxic drugs for the treatment of patients with these infections. One of these antifungal agents is the triazole fluconazole (Flu) (4,10,14,33,34,41). In vivo experimental studies suggested that Flu is active against disseminated candidiasis (8,9,29,31,32,35,37).…”

mentioning

confidence: 99%

Effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans

Etten

Rhee

Kampen

et al. 1991

Antimicrob Agents Chemother

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“…An earlier study had found that plasma levels Ͻ250 ng/ml were associated with prophylaxis failure. 20 It takes an average of 14 days of itraconazole treatment before steady-state is reached 21 but the UK study of itraconazole solution found 76% of neutropenic adult patients had serum concentrations Ͼ250 ng/ml after 7 days and 84% reached these levels after 14 days. 22 This explains the importance of starting prophylaxis at least 7 days before the onset of neutropenia.…”

Section: Discussionmentioning

confidence: 99%

Itraconazole oral solution as antifungal prophylaxis in children undergoing stem cell transplantation or intensive chemotherapy for haematological disorders

Foot

Veys

Gibson

1999

Bone Marrow Transplant

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Summary:This was an open study of oral antifungal prophylaxis in 103 neutropenic children aged 0-14 (median 5) years. Most (90%) were undergoing transplantation for haematological conditions (77% allogeneic BMT, 7% autologous BMT, 6% PBSC transplants and 10% chemotherapy alone). They received 5.0 mg/kg itraconazole/day (in 10 mg/ml cyclodextrin solution). Where possible, prophylaxis was started at least 7 days before the onset of neutropenia and continued until neutrophil recovery. Of the 103 who entered the study, 47 completed the course of prophylaxis, 27 withdrew because of poor compliance, 19 because of adverse events and 10 for other reasons. Two patients died during the study and another five died within the subsequent 30 days. No proven systemic fungal infections occurred, but 26 patients received i.v. amphotericin for antibiotic-unresponsive pyrexia. One patient received amphotericin for mycologically confirmed oesophageal candidosis. Three patients developed suspected oral candidosis but none was mycologically proven and no treatment was given. Serious adverse events (other than death) occurred in 21 patients, including convulsions (7), suspected drug interactions (6), abdominal pain (4) and constipation (4). The most common adverse events considered definitely or possibly related to itraconazole were vomiting (12), abnormal liver function (5) and abdominal pain (3). Tolerability of study medication at end-point was rated as good (55%), moderate (11%), poor (17%) or unacceptable (17%). Some patients had poor oral intakes due to mucositis. No unexpected problems of safety or tolerability were encountered. We conclude that itraconazole oral solution may be used as antifungal prophylaxis for neutropenic children. Keywords: itraconazole; mycoses; bone marrow transplantation; neutropenia; pediatrics Although advances in cytotoxic chemotherapy, stem cell transplantation and supportive care have greatly improved the survival of children with leukaemia, infections continue

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“…La asociación de tuberculosis con antiácidos, inhibidores H, AZT, 3TC, aciclovir vitamina C, culfato ferroso, ácidofólico fenitoína fluconazol diferentes tipos de micosis refleja mayor enfermedades de base y concomitantes como inmunosuoresión v mal estado aeneral del favorecedoras de la interacción. paciente; la enferkdad acidopéptica determina De los cinco pacientes con enfermedad el uso de fármacos cuya interacción sobre el acidopéptica, únicamente tres recibían trataitraconazol ha sido reconocida en otros estudios (3,9,16,(17)(18).…”

Section: Discussionunclassified

“…En los siete pacientes que recibieron rifampicina diarrea, que en casos severos pueden comprometer la administración y absorción del mismo fármaco. Es importante mencionar que aunque el itraconazol es mejor tolerado que el ketoconazol (13), los efectos gastrointestinales indeseables pueden también presentarse bajo terapia con este triazol (16).…”

Section: Discussionunclassified

lnteracciones medicamentosas en pacientes bajo tratamiento con itraconazol para diferentes tipos de micosis

Fernández¹,

Hernández²,

Londoño³

et al. 1999

biomedica

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ResumenAlgunos estudios han reportado un aumento en la frecuencia e importancia de las interacciones del itraconazol en pacientes bajo polifarmacia con fármacos que afectan el sistema enzimático de la citocromo P450 y modifican el metabolismo del azol. Con el propósito de determinar las características epidemiológicas, farmacológicas y clínicas de las interacciones medicamentosas en pacientes bajo tratamiento con itraconazol para diferentes tipos de micosis, se realizó un estudio descriptivo transversal retrospectivo en el que se analizaron 21 historias clínicas de pacientes atendidos en la Corporación para Investigaciones Biológicas durante el período 1994-1997. Entre la población estudiada, seis pacientes presentaron paracoccidioidomicosis; cinco, cromoblastomicosis; cuatro, histoplasmosis; cuatro, criptococosis, y dos, aspergilosis. En promedio, la dosis de itraconazol, la duración y el número de fármacos recibidos concomitantes fueron 223,8 mgldia, 44,3 semanas y 2,7 fármacos, respectivamente. En 10 individuos, se presentaron enfermedades de base y en 15, enfermedades concomitantes. Se documentó interacción medicamentosa (niveles no detectables o no terapéuticos de itraconazol) en 18 pacientes, de los cuales 17 presentaban sospecha clínica y 14 sospecha paraclínica de interacción. El medicamento más frecuentemente involucrado con interacción fue la rifampicina, seguido de los inhibidores H, , antiácidos y fenitoina. Similar a lo encontrado en otros estudios, la administración concomitante de estos fármacos con el itraconazol, reduce los niveles séricos de este último y altera la respuesta clínica al tratamiento. Este estudio es una aproximación inicial, aún no realizada en nuestra población, que permitirá establecer protocolos para el manejo y prevención de interacciones medicamentosas en pacientes en tratamiento con itraconazol y otros fármacos.Palabras clave: itraconazol, interacción medicamentosa. Drug interactions of itraconazole in patients under treatment for different mycoses AbstractSome studies have reported an increasing number of clinically significant interactions of itraconazole in patients receiving drugs known to have profound effects on the cytochrome P-450 enzyme system. With the purpose of determining the epidemiological, pharmacological and clinical characteristics of drug interactions in patients under therapy

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Erratum to A Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Potential in Superficial and Systemic Mycoses

Cited by 224 publications

References 0 publications

Effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans

Effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans

Itraconazole oral solution as antifungal prophylaxis in children undergoing stem cell transplantation or intensive chemotherapy for haematological disorders

lnteracciones medicamentosas en pacientes bajo tratamiento con itraconazol para diferentes tipos de micosis

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