Micafungin

2 From the Discovery of FR901379 to Clinical Studies of FK463 (Micafungin) 

Test organism FR901379 FR901381 FR901382 Aculeacin A 

5-Trichlorophenyl 4-( -octyloxy) benzoate was then obtained from 4-( -octyloxy) benzoic acid and 2,4,5-trichlorophenol using TV -dicyclohex-ylcarbodiimide in ether. The reacylation of FR179642 was then carried out using the 2,4,5-trichlorophenoyl active ester to yield FR131535. 

We tried to solve this problem by converting the central benzene ring of compound 7 into various heterocycles (Table 15.8). Initially, the reduction of 

Compound Acyl side-chain group CLOGP C. albicans FP633 A. fumiga- tus FP1305 Haemolysis  

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Solid-organ transplantation Liver transplantation Micafungin 50 mg (1 mg/kg in patients under 50 kg) IV daily Patients with two or more key risk factor Amphotericin B IV 10-20 mg daily or Liposomal amphotericin B (AmBisome) 1 mg/kg/day or flucona-... 

Echinocandin = caspofungin 70 mg loading dose, then 50 mg IV daily maintenance dose, or micafungin 100 mg daily, or anidulafungin 200 mg loading dose, then 100 mg daily maintenance dose. 

Micafungin (21 Mycamine / Funguard ) FR901379 Macrocyclic lipopeptido- lactone Semi-synthetic NP Microbial Antifungal Inhibits fungal cell wall synthesis 186, 208-210, 248-260... 

Kakeya H, Miyazaki Y, Senda H, Kobayashi T, Seki M, Izumikawa K, Yanagihara K, Yamamoto Y, Tashiro T, Kohno S. (2008) Efficacy of SPK-843, a novel polyene antifungal, in comparison with amphotericin B, liposomal amphotericin B, and micafungin against murine pulmonary aspeTgillo i. Antimicrob Agents Chemother 52 1868-1870. 

Cross S A, Scott LJ. (2008) Micafungin A review of its use in adults for the treatment of invasive and oesophageal candidiasis, and as prophylaxis against Candida infections. Drugs 68 2225-2255. 

Carter NJ, Keating GM. (2009) Micafungin A review of its use in the prophylaxis and treatment of invasive Candida infections in pediatric patients. Paediatr Drugs 11 271-291. 

Jarque I, Angel Sanz M. (2009) Micafungin in invasive candidiasis among oncohematological patients. Rev Iberoam Micol 26 75-77. 

Joseph JM, Jain R, Danziger LH. (2007) Micafungin Anew echinocandin antifungal. Pharmacotherapy 27 53-67. 

Suh B, Digumarti R, Wu C, Kovanda LL, Arnold LJ, Buell DN. (2007) Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis 45 883-893. 

Kohno S, Masaoka T, Yamaguchi H, Mori T, Urabe A, Ito A, Niki Y, Ikemoto H. (2004) A multicenter, open-label clinical study of micafungin (fk463) in the treatment of deep-seated mycosis in japan. Scand J Infect Dis 36 372-379. 

Fujie A. (2007) Discovery of micafungin (FK463) A novel antifungal derived from a novel product lead. Pure Appl Chem 79 603-614. 

Administration Administer micafungin by intravenous (IV) infusion over the period of 1 hour. More rapid infusions may result in more frequent histamine-mediated reactions. 

Note Flush an existing IV line with 0.9% sodium chloride injection prior to infusion of micafungin. 

Admixture incompatibility Do not mix or coinfuse micafungin with other medications. Micafungin has been shown to precipitate when mixed directly with a number of other commonly used medications. 

Pharmacology Micafungin is a semisynthetic lipopeptide (echinocandin) synthesized by a chemical modification of a fermentation product of Coleophoma empetri F-11899. Micafungin inhibits the synthesis of 1,3- -D-glucan, an essential component of fungal cell walls, which is not present in mammalian cells. Pharmacokinetics ... 

Pharmacokinetic Parameters of Micafungin in Adult Patients Popuiation n Dose Pharmacokinetic parameters (Mean SD )... 

The mean SD volume of distribution of micafungin at terminal phase was 0.39 0.11 L/kg body weight when determined in adult patients with esophageal candidiasis at the dose range of 50 to 150 mg. 

Micafungin is highly (more than 99%) protein bound in vitro, independent of plasma concentrations over the range of 10 to 100 mcg/mL. The primary binding protein is albumin however, micafungin, at therapeutically relevant... 

Hypersensitivity reactions - Isolated cases of serious hypersensitivity (anaphylaxis and anaphylactoid) reactions (including shock) have been reported in patients receiving micafungin. If these reactions occur, discontinue micafungin infusion and administer appropriate treatment. 

Renai function impairment Because micafungin is highly protein bound, it is not dialyzable. Supplementary dosing should not be required following hemodialysis. Pregnancy Category C. 

Lactation It is not known whether micafungin is excreted in human milk. 

Hematoiogicai effects Isolated cases of significant hemolysis and hemolytic anemia have also been reported in patients treated with micafungin. 

Hepatic effects Laboratory abnormalities in liver function tests have been seen in healthy volunteers and patients treated with micafungin. 

Renai effects Elevations in serum urea nitrogen (BUN) and creatinine, and isolated cases of significant renal dysfunction or acute renal failure have been reported in patients who received micafungin. 

Monitor patients receiving sirolimus or nifedipine in combination with micafungin for sirolimus or nifedipine toxicity, and reduce sirolimus or nifedipine dosage if necessary. 

Possible histamine-mediated symptoms have been reported with micafungin, including rash, pruritus, facial swelling, and vasodilation. 

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