Comparison of two azole antifungal drugs, ketoconazole and fluconazole, as modifiers of rat hepatic monooxygenase activity

Houston, J. Brian; Humphrey, Michael; Matthew, Diane E.; Tarbit, M. H.

doi:10.1016/0006-2952(88)90206-7

Cited by 34 publications

(5 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One report on the administra tion o f fluconazole to two pancreas recipients and one kid ney recipient in whom nephrotoxicity was a major block to the use o f amphotericin B indicated that this drug was effec tive against invasive candidiasis (which developed in two pa tients), allowing the preservation o f the transplanted organ and causing no significant adverse reactions [139]. A major advantage o f fluconazole is its minimal interference with cyclosporine; fluconazole has only a very minor effect on the hepatic cytochrome P-450 system [140][141][142], although in creased plasma levels o f cyclosporine have been reported with its use [143,144]. One im portant issue in the treatment of candidal infection with fluconazole is that certain species, such as C. krusei, exhibit a low level o f susceptibility in vitro.…”

Section: Treatmentmentioning

confidence: 99%

Fungal Infections in Solid-Organ Transplantation

Payá

1993

Clinical Infectious Diseases

355

209

View full text Add to dashboard Cite

Fungal infections following solid-organ transplantation remain a major cause of morbidity and death. Their incidence ranges from 5% among recipients of kidney transplants to as high as 40% among recipients of liver transplants. Species of Candida and Aspergillus account for more than 80% of fungal episodes. Moreover, more than 80% of fungal infections occur within the first 2 months after transplantation, with a resulting mortality of 30%-100%. The pathogenesis of infection and the risk factors involved depend on the type of transplant and the infecting microorganism. Cyclosporine has not significantly reduced the incidence or severity of fungal infections in this population. The value of surveillance cultures and fungal antigen detection in solid-organ transplant recipients remains to be determined. Amphotericin B is still a first-line drug, but its potential nephrotoxicity makes its use problematic, especially in renal transplant recipients. Fluconazole is a potential alternative for the treatment of infections due to Candida species and Cryptococcus neoformans. The role of antifungal compounds in the prophylaxis of fungal infection in recipients of solid-organ transplants needs to be established.

show abstract

Section: Treatmentmentioning

confidence: 99%

Fungal Infections in Solid-Organ Transplantation

Payá

1993

Clinical Infectious Diseases

355

209

View full text Add to dashboard Cite

show abstract

“…Since fluconazole is a weak inhibitor of certain cytochrome P-450-mediated reactions [4], it may potentiate the anticoagulant effects of warfarin and related coumarin anticoagulant drugs. The hypoglycaemic effects of tolbutamide and the sedative effects of barbiturates, may also be potentiated.…”

Section: Interactionsmentioning

confidence: 99%

Fluconazole

Vincent-Ballereau¹,

Patey²,

Lafaix³

1991

Pharmaceutisch Weekblad Scientific Edition

View full text Add to dashboard Cite

Fluconazole is a novel triazole antifungal drug chiefly used in the treatment of opportunistic mycoses in immuno-compromised patients, particularly those with the acquired immuno-deficiency syndrome (AIDS). In comparison with other antifungal drugs, fluconazole has outstanding physical and pharmacokinetic properties, such as an excellent aqueous solubility allowing a parenteral formulation, high bioavailability by the oral route, even distribution throughout the tissues, including the central nervous system and the cerebro-spinal fluid, a long half-life (permitting once daily administration), and low binding to plasma proteins. It is excreted mainly as unchanged drug in the urine. Fluconazole is a broad-spectrum antifungal agent, especially effective against Candida spp., Cryptococcus neoformans and dermatophytes. Its antifungal efficacy was mainly proved by testing in animal models, since there is no relationship between in vitro and in vivo activities. It possesses a low toxicity and it is well-tolerated. Fluconazole is currently marketed for the treatment of oropharyngeal candidiasis in immuno-compromised patients and of atrophic oral candidiasis. Its place in the treatment of opportunistic mycoses in human immuno-deficiency virus-positive patients, in particular cryptococcal meningitis, is still under investigation but is promising.

show abstract

“…(1 -2 % of patients) increased serum enzymes, above background incidence within background incidence specific for liver function (subclinical reaction) clinical liver dysfunction learned retrospectively after new drug approval: no cross-reactivity 1 in 10 000 patients particulary after prolonged therapy enzyme kinetics as well as by other publications on fluconazole (8,14,21) and itraconazole (4,7,11,16). Some of these publications are summarized in Figure 1.…”

Section: Effects Of Antimycotic Azoles On the Livermentioning

confidence: 99%

Toxicological Profile and Safety Evaluation of Antifungal Azole Derivatives

Cauteren

Lampo

Vandenberghe

et al. 1989

Mycoses

View full text Add to dashboard Cite

For the development of new systemically acting, oral antifungal azoles, it is of key importance to compare them with ketoconazole, the first available drug in this therapeutic class.Ketoconazole is a major breakthrough although hepatic side-effects as well as interactions with mammalian steroids might rarely occur during prolonged treatment. The prediction of these side-effects is difficult but the potential to interact with mammalian cytochrome P-450 enzymes is considered to be important. Therefore, for the selection of itraconazole a multidisciplinary approach was applied to study this potential. The present paper deals with the toxicological profile of itraconazole and its safety evaluation. In addition, a further comparison with ketoconazole and also with fluconazole is provided, in so far sufficient information is available.For the liver as a potential target organ, the available data indicate that itraconazole is not a predictable hepatotoxic drug in man. The major endocrine targets for overdosing with antifungal azoles are the adrenal cortex and the gonads. Endocrine studies show that itraconazole is not bearing a potential to interfere with steroid hormones in patients, which is a major improvement when compared to ketoconazole. In rats, elevation of serum cholesterol is observed especially after chronic exposure to itraconazole. This species-specific phenomenon leads at toxic dose levels to secondary events, especially in the long-term toxicity studies. In man, including those with existing hypercholesterolemia, serum cholesterol is not adversely affected by itraconazole.In pregnant rats, ketoconazole was shown to be teratogenic at high, toxic doses. The same observation has been made for itraconazole and this also might be true for fluconazole. On the other hand, all three azoles are not teratogenic in the rabbit species. Studies with itraconazole in adrenalectomized rats and in rats given exogenous arachidonic acid indicate that adrenal effects occurring at toxic dose levels are important mediators for teratogenicity. Since itraconazole does not affect adrenal function in patients, the teratogenic risk is estimated to be low.

show abstract

Comparison of two azole antifungal drugs, ketoconazole and fluconazole, as modifiers of rat hepatic monooxygenase activity

Cited by 34 publications

References 31 publications

Fungal Infections in Solid-Organ Transplantation

Fungal Infections in Solid-Organ Transplantation

Fluconazole

Toxicological Profile and Safety Evaluation of Antifungal Azole Derivatives

Contact Info

Product

Resources

About