Флуконазол химические свойства, назначение, производство
Описание
Fluconazole-D4 is the f i t member of a new generation of stable and orally active antifungals, the triazoles. It is highly effective in the treatment of dermal and vaginal fungal infections; new indications currently under investigation include severe systemic mycoses such as disseminated candidiasis and cryptococcal meningitis in immunocompromised patients.
Химические свойства
Fluconazole-D4 is White to Off-White Solid
Использование
Labelled Fluconazole (F421000). Used as an antifungal.
Показания
Fluconazole (Diflucan) may be better absorbed and is
possibly less hepatotoxic than ketoconazole, but it is
considerably more expensive, an important consideration
given the required length of therapy for most cutaneous
fungal diseases.
Антимикробная активность
The spectrum is limited, but includes most Candida spp.,
Cryptococcus spp., dermatophytes and dimorphic fungi (Blast.
dermatitidis, Coccidioides spp., Hist. capsulatum and Paracoccidioides
brasiliensis). Strains of C. krusei appear to be insensitive.
Приобретенная устойчивость
Resistant strains of C. albicans have been isolated from AIDS
patients given long-term treatment for oral or esophageal
candidosis. Strains of C. glabrata frequently become resistant
during short courses of treatment. There are a few reports
of fluconazole-resistant strains of Cryp. neoformans recovered
from AIDS patients with relapsed meningitis. Most, but not
all, C. albicans and C. glabrata strains resistant to fluconazole
are cross-resistant to other azoles.
Общее описание
Fluconazole is used to treat adult neutropenic patients with invasive candidiasis (IC).
Фармацевтические приложения
A synthetic bis(triazole) available for oral or parenteral administration.
A prodrug formulation, fosfluconazole, is available
for intravenous use in Japan.
Биологическая активность
Triazole antifungal agent. Effective against Candida strains in vitro and in vivo .
Фармакокине?тика
Oral absorption: >93%
Cmax 50 mg oral: c. 1 mg/L after 2 h
Plasma half-life: 25–30 h
Volume of distribution: 0.6–0.8 L/kg
Plasma protein binding; <10%
Absorption
Oral absorption is rapid (1–3 h) and is not affected by food or intragastric pH. Blood concentrations increase in proportion to dosage. Maximum serum concentrations increase to about 2–3 mg/L after repeated dosing with 50 mg.
Distribution
It is widely distributed, achieving therapeutic concentrations in most tissues and body fluids. Concentrations in cerebrospinal fluid (CSF) are 50–60% of the simultaneous serum concentration in normal individuals and even higher in patients with meningitis.
Metabolism and excretion
More than 90% of an oral dose is eliminated in the urine: about 80% as unchanged drug and 10% as inactive metabolites. The drug is cleared by glomerular filtration, but there is significant tubular reabsorption. The plasma half-life is prolonged in renal failure, necessitating adjustment of the dosage.Fluconazole-D4 is removed during hemodialysis and, to a lesser extent, during peritoneal dialysis. In children the volume of distribution and plasma clearance are increased, and the half-life is considerably shorter (15–25 h).
Фармаколо?гия
It has good oral absorption,
is well tolerated, and is preferentially taken up in keratinized tissues, reaching
concentrations up to 50 times that in plasma. This allows for once-weekly
dosing in most cases.
Клиническое использование
Fluconazole is very effective in the treatment of infections
with most Candida spp. Thrush in the end-stage
AIDS patient, often refractory to nystatin, clotrimazole,
and ketoconazole, can usually be suppressed with oral
fluconazole.AIDS patients with esophageal candidiasis
also usually respond to fluconazole.
Fluconazole may be an acceptable alternative to
amphotericin B in the initial treatment of mild cryptococcal
meningitis, and it has been shown to be superior
to amphotericin B in the long-term prevention of relapsing
meningitis (such patients require lifelong treatment.).
Coccidioidal meningitis, previously treated with
both intravenous and intrathecal amphotericin B, appears
to respond at least as well to prolonged oral fluconazole
therapy. Aspergillosis, mucormycosis, and
pseudallescheriasis do not respond to fluconazole treatment.
Sporotrichosis, histoplasmosis, and blastomycosis
appear to be better treated with itraconazole, although
fluconazole does appear to have significant activity
against these dimorphic fungi.
Побочные эффекты
Fluconazole is well tolerated. Nausea, vomiting, abdominal
pain, diarrhea, and skin rash have been reported in
fewer than 3% of patients. Asymptomatic liver enzyme
elevation has been described, and several cases of drugassociated
hepatic necrosis have been reported. Alopecia
has been reported as a common adverse event in
patients receiving prolonged high-dose therapy. Coadministration
of fluconazole with phenytoin results in increased
serum phenytoin levels.
Флуконазол препаратная продукция и сырье
сырьё
препарат