Ciclopirox ethanolamine

The Uses of Ciclopirox ethanolamine

Ciclopirox olamine (Loprox, Penlac) is a synthetic, broad-spectrum hydroxypyridone antifungal agent. It is chemically unrelated to the imidazoles or any other antifungal agent currently available in the United States. It appears to act through intracellular depletion of substrates and/or ions principally by inhibition of transmembrane transport of these substances. It is active against dermatophytes, yeast, and Pityrosporum orbiculare. It also demonstrates activity against Trichomonas vaginalis, some mycoplasma, and some gram-positive and gram-negative bacteria.

Indications

Ciclopirox olamine (Loprox, Penlac) is a synthetic, broad-spectrum hydroxypyridone antifungal agent. It is chemically unrelated to the imidazoles or any other antifungal agent currently available in the United States. It appears to act through intracellular depletion of substrates and/or ions principally by inhibition of transmembrane transport of these substances. It is active against dermatophytes, yeast, and Pityrosporum orbiculare. It also demonstrates activity against Trichomonas vaginalis, some mycoplasma, and some gram-positive and gram-negative bacteria.

Manufacturing Process

Ciclopirox may be produced as follows: 2 g of 4-methyl-6-cyclohexyl-2-pyrone were heated with 1 g of hydroxylamine hydrochloride and 5 g of 2-
aminopyridine to 80 C for 8 hours. The reaction mixture was then dissolved in methylene chloride, the amine was removed by shaking with dilute hydrochloric acid, the reaction product was extracted from the organic phase by means of dilute sodium hydroxide solution and the alkaline solution was acidified with acetic acid to a pH value of 6. The 1-hydroxy-4-cnethyl-6-cyclohexyl-2-pyridone precipitated in crystalline form. It was filtered off with suction, washed with water and dried. The yield was 1.05 g (49% of theory); melting point 143 C. Reaction of ciclopirox with ethanolamine gives the desired prod

Biological Activity

ciclopirox ethanolamine, working as an iron chelator, suppresses a substantial number of clinically relevant dermatophytes, yeasts, and molds, including the frequently azole-resistant candida species candida glabrata, candida krusei, and candida guilliermondii. moreover, ciclopirox has been proved to inhibit a wide range of bacteria in humans, including many gram-positive and gram-negative species pathogenic bacteria. [1]

Safety Profile

Poison by intravenous andintraperitoneal routes. Moderately toxic by ingestion andsubcutaneous routes. Experimental reproductive effects.When heated to decomposition it emits toxic fumes ofNOx.

Side Effects

Common side effects include local skin irritation, rash, dryness, and peeling. Severe allergic reactions are rare but require immediate medical attention.

Mechanism

Ciclopirox exerts its action by binding to and chelating trivalent cations, such as Fe3+ and Al3+, thereby inhibiting the availability of essential co-factors for enzymes. This may lead to a loss of activity of enzymes that are essential for cellular metabolism, organization of cell wall structure and other crucial cell functions. In addition, ciclopirox exerts its anti-inflammatory activity by inhibiting 5-lipoxygenase and cyclooxygenase (COX).

References

[1]niewerth m, kunze d, seibold m, schaller m, korting hc and hube b. ciclopirox olamine treatment affects the expression pattern of candida albicans genes encoding virulence factors, iron metabolism proteins, and drug resistance factors. antimicrob agents chem. 2003 jun; 47(6): 180517.
[2]linden t, katschinski dr, eckhardt k, scheid a, pagel h and wenger rh. the antimycotic ciclopirox olamine induces hif-1 stability, vegf expression, and angiogenesis. faseb. 2003 feb; 17: 761–3.
[3]subissi a, monti d, togni g and mailland f. recent nonclinical and clinical data relevant to its use as a topical antimycotic agent. drugs. 2010 nov; 70(16): 2133-52.