Population Pharmacokinetic Analysis of Micafungin in Japanese Patients with Fungal Infections

Tabata, Kenji; Katashima, Masataka; Kawamura, Akio; Kaibara, Atsunori; Tanigawara, Yusuke

doi:10.2133/dmpk.21.324

Cited by 26 publications

(22 citation statements)

References 12 publications

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“…Further investigations in the patients with higher T. bil level may be required. Concerning kidney function, we found that the plasma concentrations of MCFG, were not influenced by the parameters of kidney function as has been reported in population pharmacokinetic study (17) and by Shimoeda et al (16). Although protein binding of MCFG in human serum and plasma is reported to be 99.8%, (13,18) there was no relationship between the plasma concentrations of MCFG and serum albumin levels.…”

Section: Discussionsupporting

confidence: 81%

Effect of liver and kidney function on migafungin disposition in patients with hematologic malignancies

Nakagawa

Ichii

Saeki

et al. 2008

Eur. J. Drug Metabol. Pharmacokinet.

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The plasma concentration of micafungin (MCFG) after intravenous infusion of MCFG at 150 or 300 mg/day over 1 hour to 49 patients with hematologic malignancies were determined, and the relationship between the plasma concentrations and the patients' laboratory parameters of liver and kidney function was analyzed. Plasma samples were obtained at the end of the initial administration of MCFG, 5 to 6 hours after the start of the initial administration, immediately before the second dosing, immediately before the fourth dosing, and the end of the fourth dosing. The plasma concentration of MCFG was measured by high performance liquid chromatography. The plasma concentration of MCFG was correlated with the doses of MCFG per kilogram body weight. The peak concentration after the initial administration was 3.8 times higher than the trough level after the initial administration. The steady-state peak and trough levels were 1.4-1.5 times higher than those after the initial administration. There was no correlation between the laboratory parameters of liver/kidney function and the dose-normalized plasma concentration of MCFG. These results suggest that MCFG can be administered safely to patients with liver or kidney dysfunction without adjusting the dose.

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Section: Discussionsupporting

confidence: 81%

Effect of liver and kidney function on migafungin disposition in patients with hematologic malignancies

Nakagawa

Ichii

Saeki

et al. 2008

Eur. J. Drug Metabol. Pharmacokinet.

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“…Burn injury affects many organ systems throughout the body, resulting in complex pathophysiological changes, including changes in plasma protein levels (8). In this study, no obvious relationships between the plasma MCFG concentrations and the laboratory parameters for hepatic and renal function, serum albumin, surgical operation, and continuous hemodiafiltration were observed (Table 1), similar to data in previous reports (7,9,11,16). On the other hand, the distribution volume in patients with burns is known to be altered by changes in the extracellular fluid volume (8).…”

supporting

confidence: 90%

Micafungin Concentrations in the Plasma and Burn Eschar of Severely Burned Patients

Sasaki¹,

Yamanouchi²,

Kudo³

et al. 2012

Antimicrob Agents Chemother

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Micafungin concentrations in plasma and burn eschar after daily intravenous infusion (1 h) of micafungin (200 to 300 mg) were investigated for six patients with severe burns. Micafungin treatment was initiated more than 72 h after the burn injuries. The peak and trough levels in the plasma after the initial administration and repeated administrations for more than 4 days were comparable with or slightly lower than the reported values for healthy volunteers. Micafungin concentrations in the plasma and burn eschar were between 3.6 and >1,000 times higher than the reported MIC 90 s of micafungin against clinically important Candida and Aspergillus species.

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“…In a population-based pharmacokinetic analysis using pediatric and adult patients, neither hematocrit nor serum albumin concentration was selected as a contributory factor for total body clearance of MCFG (Tabata et al 2006). The present study therefore provided experimental evidence using a rat model supporting the previous clinical findings.…”

Section: Discussionsupporting

confidence: 65%

Effect of blood decrease on micafungin disposition in rats

Konishi

Fukushima

Sudo

et al. 2011

Eur J Drug Metab Pharmacokinet

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Micafungin (MCFG) is a novel echinocandin-class antifungal agent that extensively undergoes metabolic removal in the liver. In the present study, the influence of decreased blood volume on pharmacokinetic disposition of MCFG was examined using a rat model prepared by phlebotomy. In phlebotomized rats, hematocrit level and plasma albumin concentration were decreased by 50 and 15%, respectively. Regarding the pharmacokinetic parameters of MCFG, there were no significant differences in the total body clearance (CL(tot)) and elimination rate constant (k (e)) between control and phlebotomized rat groups. A slight increase was observed in the apparent volume of distribution at steady-state (Vd(ss)), but the degree of change was minimal. These findings demonstrate that the elimination capacity for MCFG is only slightly affected by severe anemia and moderate hypoalbuminemia, and provide experimental evidence for the preceding clinical studies suggesting that neither hematocrit level nor serum albumin concentration is a contributory factor for the metabolic clearance of MCFG.

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Population Pharmacokinetic Analysis of Micafungin in Japanese Patients with Fungal Infections

Cited by 26 publications

References 12 publications

Effect of liver and kidney function on migafungin disposition in patients with hematologic malignancies

Effect of liver and kidney function on migafungin disposition in patients with hematologic malignancies

Micafungin Concentrations in the Plasma and Burn Eschar of Severely Burned Patients

Effect of blood decrease on micafungin disposition in rats

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