The screening of these selected molecules randomly chosen produced no antifungal activity pharmacologically relevant whatever the species of Candida used (C albicans, C parapsilosis and C glabrata with MIC values systematically higher than 10(jLg/ml (data not shown) whereas the drug control 5-fluorocytosine
gave an MIC of 0.
These expressions target clinicalSignificance and specimen where specimenType is serum in the 5-fluorocytosine
Ifosfamide is activated by cytochrome p450 enzymes to form phosphoramide mustard and acrolein, and 5-fluorocytosine
is activated by the enzyme cytosine deaminase to form 5-fluorouracil (5-FU).
was moderately active to S.
There have been only two reports of successful treatment--one with a combination of IV pentamidine and oral itraconazole and the other with 5-fluorocytosine
Then the prodrug-activating enzyme produced in the cancer cell is designed to activate orally administered Toca FC, an investigational extended-release formulation of 5-fluorocytosine
(5-FC), into a powerful antimetabolite, 5CaeFU, which kills the infected cancer cell and neighboring 5-FU sensitive tumor cells.
In vitro activities of 5-fluorocytosine
against 8,803 clinical isolates of Candida spp.
62 [micro]g/mL) and relatively resistant to 5-fluorocytosine
Then the prodrug-activating enzyme produced in the cancer cell activates orally administered Toca FC, an extended-release formulation of 5-fluorocytosine
(5-FC), into a powerful antimetabolite, 5-FU, selectively in the cancer cell.
MICs (mg/L) were >16 for amphotericin B, >64 for fluconazole, >8 for itraconazole, >64 for 5-fluorocytosine
, and >16 for ketoconazole, 2-8 for voriconazole, and 1-4 for terbinafine.
Prodrug-activating enzymes that have been used in this approach include cytosine deaminase, which catalyzes the conversion of the nontoxic 5-fluorocytosine
to the cytotoxic 5-fluorouracil, and herpes simplex virus thymidine kinase, which, together with cellular enzymes, facilitates the conversion of ganciclovir into the toxic ganciclovir triphosphate.
Toca 511 & Toca FC, an extended-release formulation of 5-fluorocytosine
(5-FC), is designed to have a dual mechanism of action.