Flucytosine excretion

Flucytosine Interferes with DNA and RNA synthesis selectively in fungi Synergistic with amphotericin systemic toxicity in host due to DNA and RNA effects Cryptococcus and chromoblastomycosis infections Oral duration, hours renal excretion Toxicity Myelosuppression... 

Flucytosine (Ancobon) possesses clinically useful activity against Cryptococcus neoformans, Candida species, Torulopsis glabrata, and the agents of chromomycosis. Susceptible fungi deam-inate flucytosine to 5-fluorouracil, which becomes an antimetabolite. Flucytosine, which is excreted by the kidney, should be used cautiously in the setting of renal impairment. Flucytosine is a bone marrow depressant. Flucytosine is used in combination with amphotericin B. 

Pharmacokinetics Flucytosine is well absorbed by the oral route, distributes throughout the body water, and penetrates well into cerebrospinal fluid (CSF). 5-Fluorouracil is detectable in patients and probably is due to metabolism of 5-FC by intestinal bacteria. Excretion of both the parent drug and its metabolites is by glomerular filtration, and the dose must be adjusted in patients with compromised renal function. 

AMPHOTERICIN ANTI FUNG ALS -FLUCYTOSINE t flucytosine levels, with risk of toxic effects Amphotericin causes 1 renal excretion of flucytosine and t cellular uptake The combination of flucytosine and amphotericin may be used therapeutically. Watch for early features of flucytosine toxicity (gastrointestinal upset) monitor renal and liver function closely... 

Flucytosine (5-fluorocytosine) is metabolised in the fungal cell to 5-fluorouracil which inhibits nucleic acid synthesis. It is weU absorbed from the gut, penetrates effectively into tissues and almost all is excreted unchanged in the urine (t) 4 h). The dose should be reduced for patients with impaired renal function, and the plasma concentration should be monitored. The drug is well tolerated when renal function is normal. Candida albicans rapidly becomes resistant to flucytosine which ought not to be used alone it may be combined with amphotericin (see Table 14.2) but this increases the risk of adverse effects (leucopenia, thrombocytopenia, enterocolitis) and it is reserved for serious infections where the risk-benefit balance is favourable (e.g. Cryptococcus neoformans meningitis). 

Zidovudine is rapidly absorbed from the G1 tract with peak serum concentrations occurring within 30 to 90 minutes. It binds to plasma proteins to the extent of 35 to 40%. Zidovudine is rapidly metabolized in the liver to the inactive 3 -azido-3 -deoxy-5 -0-beta-D-glucopyranuronosylthymi-dine (GAZT), which has an apparent elimination half-life of 1 hour. Zidovudine undergoes glomerular filtration and active tubular secretion. Coadministration of zidovudine with agents such as dapsone, pentamidine, amphotericin B, flucytosine, vincristine, vinblastine, adriamycin, and interferon with potential to cause nephrotoxicity or cytotoxicity to hematopoietic elements, enhance its risk of adverse effects. Probenecid will inhibit the renal excretion of zidovudine. 

Flucytosine is absorbed rapidly and well from the GI tract, widely distributed, and minimally bound to plasma proteins. Flucytosine concentration in CSF is 65—90% of that found simultaneously in plasma. Approximately 80% of a dose is excreted unchanged in the urine. The tj of the drug normally is 3-6 hours but may reach 200 hours in renal failure. Dose modification is necessary in patients with decreased renal junction, and plasma concentrations should be measured periodically to maintain peak concentrations of50—100 fig/mL. Flucytosine is cleared by hemodialysis, and patients should receive a single dose of 37.5 mg/kg after dialysis the drug also is removed by peritoneal dialysis. 

Flucytosine is usually administered intravenously over 20 to 40 minutes. Protein binding is low (approximately 2-4%) and volume of distribution is high (0.7-1 L/kg) with cerebrospinal fluid (CSF) concentrations comparable to serum concentrations. Approximately 90% of a dmg dose is excreted unchanged in the urine. The dmg has a half-life of 3-6 hours in adult patients with normal renal function. Patients with renal impairment should be given smaller doses which can be estimated according to their creatinine clearance. Only a small percentage of flucytosine is metabolised to 5-fluorouracil by the body, with an area under... 

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