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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Itraconazole is an orally administered triazole antifungal agent. Its spectrum of activity includes dermatophyte, dimorphic and dematiaceous fungi, yeasts, and some moulds. In clinical trials, mycological cure was attained in approximately 70 to 80, > or = 70 and > or = 80% of patients with, respectively, fingernail and toenail onychomycosis (200 mg/day for 3 months), dermatophytosis (100 mg/day for 2 to 4 weeks) and vaginal candidiasis (400 mg/day for 1 day or 200 mg/day for 3 days). Approximately 20 to 30% of patients with onychomycosis may relapse after completion of therapy; relapse rate data are limited for the other indications. Recently developed intermittent regimens of itraconazole (400 mg/day for 1 week per month for 3 to 4 months) appear to have similar efficacy to standard regimens in the treatment of onychomycosis. Shorter, higher dosage itraconazole treatment regimens (200 or 400 mg/day for 1 week) are also beneficial in dermatomycoses. Discrepancies and limitations of study design hamper conclusions about efficacy relative to other antifungal drugs. Newer intermittent and short course higher dosage itraconazole regimens have also not been evaluated in comparative studies. Available studies show that the efficacy of itraconazole appears to be greater than that of griseofulvin, but similar to or lower than that of terbinafine in patients with dermatophyte onychomycosis or cutaneous fungal infections. Moreover, the efficacy of itraconazole may be similar to or lower than that of fluconazole in the treatment of cutaneous mycoses. Comparative data from patients with acute vaginal candidiasis suggest that itraconazole is at least as effective as intravaginal clotrimazole and oral fluconazole, and superior to intravaginal econazole. These results require confirmation. Prescription-event monitoring data indicate that itraconazole is generally well tolerated. Gastrointestinal disturbances, dizziness and headache occur most commonly; liver toxicity has been rarely described. Its usefulness in some clinical situations may be limited because of its ability to interact with various therapeutic agents. In conclusion, itraconazole along with other established agents should be considered a first-line treatment for patients with extensive or recalcitrant cutaneous fungal infections, mixed dermatophyte and Candida onychomycosis or vaginal candidiasis. It is currently considered a second-line drug for dermatophyte onychomycosis; the use of newer intermittent itraconazole treatment regimens may, however, extend its role in the management of this condition. Although itraconazole offers greater benefit than conventional therapies (griseofulvin and ketoconazole) in terms of efficacy and tolerability, wider clinical experience is required to determine its merits relative to the newer agents, terbinafine and fluconazole.
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PMID:Itraconazole. A reappraisal of its pharmacological properties and therapeutic use in the management of superficial fungal infections. 870 96

Itraconazole is a new triazole compound with a broad spectrum of activity against a number of fungal pathogens, including Aspergillus species. The drug is being used increasingly as prophylaxis in patients with immunodepression. Itraconazole is highly lipophilic and only ionised at low pH. The absolute availability of capsules in healthy volunteers under fasting conditions is about 55% and is increased after a meal. Itraconazole is 99.8% bound to human plasma proteins and its apparent volume of distribution is about 11 L/kg. The drug is extensively metabolised by the liver. Among the metabolites, hydroxy-itraconazole is of particular interest because its antifungal activity measured in vitro is similar to that of the parent drug and its plasma concentration is 2 to 3 times higher than that of itraconazole. Mean total itraconazole blood clearance determined in healthy volunteers following a single intravenous infusion was 39.6 L/h. After a single oral dose, the terminal elimination half-life of itraconazole is about 24 hours. The drug exhibits a dose-dependent pharmacokinetic behaviour. Renal failure does not affect the pharmacokinetic properties of itraconazole; however, little is known about the effects of hepatic insufficiency. In immunocompromised patients the absorption of itraconazole is affected by gastrointestinal disorders caused by diseases and cytotoxic chemotherapy. The pharmacokinetics of itraconazole may be significantly altered when the drug is coadministered with certain other agents. Itraconazole is a potent inhibitor of cytochrome P450 (CYP) 3A4 and, thus, can also considerably change the pharmacokinetics of other drugs. Such changes may have clinically relevant consequences. Itraconazole appears to be well tolerated. Gastrointestinal disturbances and dizziness are the most frequently reported adverse effects. Clinical studies in patients with haemotological malignancies suggest that plasma concentrations [measured by high performance liquid chromatography (HPLC)] > or = 250 micrograms/L itraconazole, or 750 to 1000 micrograms/L for itraconazole plus hydroxy-itraconazole, are required for effective prophylactic antifungal activity. It seems that a curative effect may be enhanced by ensuring that itraconazole plasma concentrations exceed 500 micrograms/L. The marked intra- and inter-patient variability in the pharmacokinetics of the drug, and the fact that it is impossible to predict steady-state plasma concentrations from the initial dosage are major factors obscuring any clear relationship between dose and plasma concentrations and clinical efficacy. Thus, in patients with life-threatening fungal infections treated with itraconazole drug, plasma concentrations should be regularly monitored to ensure sufficient drug exposure for antifungal activity.
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PMID:Optimisation of itraconazole therapy using target drug concentrations. 988 17