Pharmacokinetics of Micafungin in Healthy Volunteers, Volunteers With Moderate Liver Disease, and Volunteers With Renal Dysfunction

Hébert, Mary F.; Smith, Helen; Marbury, Thomas; Swan, Suzanne K.; Smith, William B.; Townsend, Robert; Buell, Donald N.; Keirns, James J.; Bekersky, Ihor

doi:10.1177/0091270005279580

Cited by 157 publications

(152 citation statements)

References 20 publications

(20 reference statements)

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“…14) Several reports have demonstrated that MCFG is a safe and effective antifungal agent, 9,[15][16][17] suggesting that dose adjustment is not required for elderly patients or patients with moderate liver dysfunction or severe kidney dysfunction. 9,12) However, information on the efficacy and safety of MCFG for the treatment of fungal infections in LDLT-recipients has been limited due to the small sample sizes of the studies reported previously [18][19][20] ; i.e., less than 9 LDLT-recipients in each study. In addition, there have been no reports concerning the efficacy and safety of MCFG in patients with severe liver dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…9,12) However, little is known about the pharmacokinetic or pharmacodynamic changes of MCFG in LDLT-recipients with extremely unstable liver function. In the present study, we measured the plasma concentration of MCFG in 20 recipients of LDLT and evaluated the clinical effects and safety of MCFG using biochemical parameters.…”

Section: )mentioning

confidence: 99%

“…6) Furthermore, other reports have concluded that dose adjustment is not required for elderly patients or patients with moderate liver dysfunction or severe renal dysfunction. 9,12) However, little is known about the pharmacokinetic or pharmacodynamic changes of MCFG in LDLT-recipients with extremely unstable liver function. In the present study, we measured the plasma concentration of MCFG in 20 recipients of LDLT and evaluated the clinical effects and safety of MCFG using biochemical parameters.…”

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confidence: 99%

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The Impact of Total Bilirubin on Plasma Micafungin Levels in Living-Donor Liver Transplantation Recipients with Severe Liver Dysfunction

Iwamoto

Kagawa

Sakurai

et al. 2009

Biological & Pharmaceutical Bulletin

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Mcafungin (MCFG) is a semisynthetic antifungal echinocandin-like lipopeptide that inhibits the synthesis of 1,3-b-D-glucan, an essential polymeric polysaccharide in the cell wall of many pathogenic fungi.1,2) MCFG has superior antibacterial activity against Candida and Aspergillus species.3) Currently, this agent is commonly administered to prevent and treat deep-seated mycosis in patients with various diseases. [4][5][6][7][8] It is also administered to recipients of living-donor liver transplantations (LDLT) to prevent or treat invasive fungal infections. MCFG is metabolized primarily by sulfatase and cytochrome P450, and has low hepatic extraction ratio. Additionally, MCFG has very high protein binding (Ͼ99.5%) in plasma and 90% of MCFG administered and its metabolites are eliminated through the bile. 9)It is reported that MCFG has low mechanism-based toxicity because the inhibition of fungal cell wall synthesis effected by echinocandins has no relevance for mammalian cells.10,11) MCFG was reported to be well tolerated at doses from 2.5 to 150 mg/d in healthy male volunteers, suggesting that MCFG could be administered safely to most patients. 6)Furthermore, other reports have concluded that dose adjustment is not required for elderly patients or patients with moderate liver dysfunction or severe renal dysfunction. 9,12) However, little is known about the pharmacokinetic or pharmacodynamic changes of MCFG in LDLT-recipients with extremely unstable liver function. In the present study, we measured the plasma concentration of MCFG in 20 recipients of LDLT and evaluated the clinical effects and safety of MCFG using biochemical parameters. MATERIALS AND METHODS PatientsThe subjects in this study were 20 patients who visited the Department of Hepatobiliary Pancreatic Surgery of Mie University Hospital between April 2003 and March 2007. After receiving a LDLT, these patients were diagnosed with fungal infections according to a rise in b-D-glucan (BDG) or a positive reaction to an Aspergillus antigen. Written informed consent was obtained for this study from all subjects or their families. In addition, the Ethics Committee of our university gave its approval for this study. MCFG Infusion and Blood SamplingThe subjects received MCFG as treatment for their fungal infections. MCFG was administered by a constant infusion for 60 min via a peripheral venous catheter, once daily, at doses of 100-300 mg. When the blood MCFG concentration reached a steady state, the patient's blood samples were taken before (trough) and an hour after (peak) the drip infusion of MCFG. The blood was centrifuged at 2100ϫg for 20 min at room temperature, and the plasma was separated and kept at Ϫ80°C until analysis.Determination of Plasma Micafungin MCFG solution (100 mg/ml) and FR195743 solution (internal standard (IS); 100 mg/ml) were donated by Astellas Pharma Inc. (Tokyo). All other reagents were of the highest grade available. The plasma concentrations of MCFG were determined by high performance liquid chromatography (HPLC) according to the ...

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Section: Discussionmentioning

confidence: 99%

Section: )mentioning

confidence: 99%

mentioning

confidence: 99%

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The Impact of Total Bilirubin on Plasma Micafungin Levels in Living-Donor Liver Transplantation Recipients with Severe Liver Dysfunction

Iwamoto

Kagawa

Sakurai

et al. 2009

Biological & Pharmaceutical Bulletin

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“…103 Arylsulfatase is involved in micafungin metabolism, 104 and polymorphisms have been described. 105 In general, however, pharmacogenomic analysis seems unlikely to add much to the clinical use of micafungin.…”

Section: Echinocandinsmentioning

confidence: 99%

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

Ashbee

Gilleece

2011

Bone Marrow Transplant

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“…No dosage adjustment is necessary in renal failure or haemodialysis [57,58]. During pregnancy it should be used with caution (category C).…”

Section: Pharmacokinetics and Adverse Eventsmentioning

confidence: 99%

New antifungal agents for the treatment of candidaemia

Muñóz¹,

Guinea²,

Rojas³

et al. 2010

International Journal of Antimicrobial Agents

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Suspected or proven invasive candidiasis is an important indication for antifungal drugs and a leading cause of death. Prompt initiation of effective therapy has a marked effect on survival, but the indiscriminate application of different risk factorbased prediction models is massively increasing the number of patients treated unnecessarily. Fluconazole resistance levels are <5% in most European centres and the use of low doses is still common. Candins are fungicidal, have efficacy against device-related infections, have few interactions and are well tolerated. Accordingly, the use of newer, more expensive drugs must be carefully balanced in each case.Campaigns directed towards stewardship in antifungal drug use must take into consideration the choice of the drug, the dose and route of administration, and the length of therapy. Early microbiological information and medical education may contribute to better use of these important drugs. We review the characteristics of the new antifungals used for the treatment of candidaemia.

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Pharmacokinetics of Micafungin in Healthy Volunteers, Volunteers With Moderate Liver Disease, and Volunteers With Renal Dysfunction

Cited by 157 publications

References 20 publications

The Impact of Total Bilirubin on Plasma Micafungin Levels in Living-Donor Liver Transplantation Recipients with Severe Liver Dysfunction

The Impact of Total Bilirubin on Plasma Micafungin Levels in Living-Donor Liver Transplantation Recipients with Severe Liver Dysfunction

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

New antifungal agents for the treatment of candidaemia

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