Skip to main content
Erschienen in: European Journal of Drug Metabolism and Pharmacokinetics 1/2011

01.03.2011 | Original Paper

Effect of blood decrease on micafungin disposition in rats

verfasst von: Hiroki Konishi, Keizo Fukushima, Masatomo Sudo, Masaki Sumi, Tokuzo Minouchi, Ikumi Iga, Nobuhito Shibata, Akira Yamaji

Erschienen in: European Journal of Drug Metabolism and Pharmacokinetics | Ausgabe 1/2011

Einloggen, um Zugang zu erhalten

Abstract

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 (CLtot) 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 (Vdss), 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.
Literatur
Zurück zum Zitat Abe F, Ueyama J, Kawasumi N et al (2008) Role of plasma proteins in pharmacokinetics of micafungin, an antifungal antibiotic, in analbuminemic rats. Antimicrob Agents Chemother 52:3454–3456PubMedCrossRef Abe F, Ueyama J, Kawasumi N et al (2008) Role of plasma proteins in pharmacokinetics of micafungin, an antifungal antibiotic, in analbuminemic rats. Antimicrob Agents Chemother 52:3454–3456PubMedCrossRef
Zurück zum Zitat Azuma J, Nakahara K, Kagayama A, Kajiho T, Kawamura A, Suematsu H, Mukai T (2002) Phase I study of micafungin. Jpn J Chemother 50:S104–S147 Azuma J, Nakahara K, Kagayama A, Kajiho T, Kawamura A, Suematsu H, Mukai T (2002) Phase I study of micafungin. Jpn J Chemother 50:S104–S147
Zurück zum Zitat Chandrasekar PH, Sobel JD (2006) Micafungin: a new echinocandin. Clin Infect Dis 42:1171–1178PubMedCrossRef Chandrasekar PH, Sobel JD (2006) Micafungin: a new echinocandin. Clin Infect Dis 42:1171–1178PubMedCrossRef
Zurück zum Zitat Dager WE, Inciardi JF, Howe TL (1995) Estimating phenytoin concentrations by the Sheiner-Tozer method in adults with pronounced hypoalbuminemia. Ann Pharmacother 29:667–670PubMed Dager WE, Inciardi JF, Howe TL (1995) Estimating phenytoin concentrations by the Sheiner-Tozer method in adults with pronounced hypoalbuminemia. Ann Pharmacother 29:667–670PubMed
Zurück zum Zitat DiPiro JT, Hooker KD, Sherman JC, Gaines MG, Wynn JJ (1992) Effect of experimental hemorrhagic shock on hepatic drug elimination. Crit Care Med 20:810–815PubMedCrossRef DiPiro JT, Hooker KD, Sherman JC, Gaines MG, Wynn JJ (1992) Effect of experimental hemorrhagic shock on hepatic drug elimination. Crit Care Med 20:810–815PubMedCrossRef
Zurück zum Zitat Dubniks M, Persson J, Grände PO (2007) Plasma volume expansion of 5% albumin, 4% gelatin, 6% HES 130/0.4, and normal saline under increased microvascular permeability in the rat. Intensive Care Med 33:293–299PubMedCrossRef Dubniks M, Persson J, Grände PO (2007) Plasma volume expansion of 5% albumin, 4% gelatin, 6% HES 130/0.4, and normal saline under increased microvascular permeability in the rat. Intensive Care Med 33:293–299PubMedCrossRef
Zurück zum Zitat Fradette C, Du Souich P (2004) Effect of hypoxia on cytochrome P450 activity and expression. Curr Drug Metab 5:257–271PubMedCrossRef Fradette C, Du Souich P (2004) Effect of hypoxia on cytochrome P450 activity and expression. Curr Drug Metab 5:257–271PubMedCrossRef
Zurück zum Zitat Hatano K, Morishita Y, Nakai T, Ikeda F (2002) Antifungal mechanism of FK463 against Candida albicans and Aspergillus fumigatus. J Antibiot 55:219–222PubMed Hatano K, Morishita Y, Nakai T, Ikeda F (2002) Antifungal mechanism of FK463 against Candida albicans and Aspergillus fumigatus. J Antibiot 55:219–222PubMed
Zurück zum Zitat Hebert MF, Smith HE, Marbury TC et al (2005) Pharmacokinetics of micafungin in healthy volunteers, volunteers with moderate liver disease, and volunteers with renal dysfunction. J Clin Pharmacol 45:1145–1152PubMedCrossRef Hebert MF, Smith HE, Marbury TC et al (2005) Pharmacokinetics of micafungin in healthy volunteers, volunteers with moderate liver disease, and volunteers with renal dysfunction. J Clin Pharmacol 45:1145–1152PubMedCrossRef
Zurück zum Zitat Hiemenz J, Cagnoni P, Simpson D et al (2005) Pharmacokinetic and maximum tolerated dose study of micafungin in combination with fluconazole versus fluconazole alone for prophylaxis of fungal infections in adult patients undergoing a bone marrow or peripheral stem cell transplant. Antimicrob Agents Chemother 49:1331–1336PubMedCrossRef Hiemenz J, Cagnoni P, Simpson D et al (2005) Pharmacokinetic and maximum tolerated dose study of micafungin in combination with fluconazole versus fluconazole alone for prophylaxis of fungal infections in adult patients undergoing a bone marrow or peripheral stem cell transplant. Antimicrob Agents Chemother 49:1331–1336PubMedCrossRef
Zurück zum Zitat Johnson KB, Egan TD, Kern SE et al (2003) The influence of hemorrhagic shock on propofol: a pharmacokinetic and pharmacodynamic analysis. Anesthesiology 99:409–420PubMedCrossRef Johnson KB, Egan TD, Kern SE et al (2003) The influence of hemorrhagic shock on propofol: a pharmacokinetic and pharmacodynamic analysis. Anesthesiology 99:409–420PubMedCrossRef
Zurück zum Zitat Joseph JM, Jain R, Danziger LH (2007) Micafungin: a new echinocandin antifungal. Pharmacotherapy 27:53–67PubMedCrossRef Joseph JM, Jain R, Danziger LH (2007) Micafungin: a new echinocandin antifungal. Pharmacotherapy 27:53–67PubMedCrossRef
Zurück zum Zitat Kaneko H, Yamato Y, Teramura Y et al (2002) Metabolites of micafungin in rats and dogs. Jpn J Chemother 50:S88–S93 Kaneko H, Yamato Y, Teramura Y et al (2002) Metabolites of micafungin in rats and dogs. Jpn J Chemother 50:S88–S93
Zurück zum Zitat Konishi H, Sudo M, Sumi M, Morii H, Minouchi T, Aimoto T, Yamaji A (2005) Pharmacokinetic behavior of micafungin in rats with carbon tetrachloride-induced acute hepatic failure. Biol Pharm Bull 28:556–559PubMedCrossRef Konishi H, Sudo M, Sumi M, Morii H, Minouchi T, Aimoto T, Yamaji A (2005) Pharmacokinetic behavior of micafungin in rats with carbon tetrachloride-induced acute hepatic failure. Biol Pharm Bull 28:556–559PubMedCrossRef
Zurück zum Zitat Konishi H, Fukushima K, Sudo M et al (2010) Reduced elimination clearance of micafungin in rats with cholestatic hyperbilirubinemia. Fundam Clin Pharmacol 24:457–462PubMedCrossRef Konishi H, Fukushima K, Sudo M et al (2010) Reduced elimination clearance of micafungin in rats with cholestatic hyperbilirubinemia. Fundam Clin Pharmacol 24:457–462PubMedCrossRef
Zurück zum Zitat McLean AJ, Morgan DJ (1991) Clinical pharmacokinetics in patients with liver disease. Clin Pharmacokinet 21:42–69PubMedCrossRef McLean AJ, Morgan DJ (1991) Clinical pharmacokinetics in patients with liver disease. Clin Pharmacokinet 21:42–69PubMedCrossRef
Zurück zum Zitat Numeroso F, Barilli AL, Delsignore R (2008) Prevalence and significance of hypoalbuminemia in an internal medicine department. Eur J Intern Med 19:587–591PubMedCrossRef Numeroso F, Barilli AL, Delsignore R (2008) Prevalence and significance of hypoalbuminemia in an internal medicine department. Eur J Intern Med 19:587–591PubMedCrossRef
Zurück zum Zitat Saavedra S, Jarque I, Sanz G et al (2002) Infectious complications in patients undergoing unrelated donor bone marrow transplantation: experience from a single institution. Clin Microbiol Infect 8:725–733PubMedCrossRef Saavedra S, Jarque I, Sanz G et al (2002) Infectious complications in patients undergoing unrelated donor bone marrow transplantation: experience from a single institution. Clin Microbiol Infect 8:725–733PubMedCrossRef
Zurück zum Zitat Shibata N, Shimakawa H, Minouchi T, Yamaji A (1993) Pharmacokinetics of cyclosporin A after intravenous administration to rats in various disease states. Biol Pharm Bull 16:1130–1135PubMed Shibata N, Shimakawa H, Minouchi T, Yamaji A (1993) Pharmacokinetics of cyclosporin A after intravenous administration to rats in various disease states. Biol Pharm Bull 16:1130–1135PubMed
Zurück zum Zitat Tabata K, Yamaoka K, Kaibara A, Suzuki S, Terakawa M, Hata T (1999) Moment analysis program available on Microsoft Excel®. Xenobio Metabol Dispos 14:286–293 Tabata K, Yamaoka K, Kaibara A, Suzuki S, Terakawa M, Hata T (1999) Moment analysis program available on Microsoft Excel®. Xenobio Metabol Dispos 14:286–293
Zurück zum Zitat Tabata K, Katashima M, Kawamura A, Kaibara A, Tanigawara Y (2006) Population pharmacokinetic analysis of micafungin in Japanese patients with fungal infections. Drug Metab Pharmacokinet 21:324–331PubMedCrossRef Tabata K, Katashima M, Kawamura A, Kaibara A, Tanigawara Y (2006) Population pharmacokinetic analysis of micafungin in Japanese patients with fungal infections. Drug Metab Pharmacokinet 21:324–331PubMedCrossRef
Zurück zum Zitat Tomishima M, Ohki H, Yamada A, Takasugi H, Maki K, Tawara S, Tanaka H (1999) FK463, a novel water-soluble echinocandin lipopeptide: synthesis and antifungal activity. J Antibiot 52:674–676PubMed Tomishima M, Ohki H, Yamada A, Takasugi H, Maki K, Tawara S, Tanaka H (1999) FK463, a novel water-soluble echinocandin lipopeptide: synthesis and antifungal activity. J Antibiot 52:674–676PubMed
Zurück zum Zitat Torres HA, Bodey GP, Rolston KV, Kantarjian HM, Raad II, Kontoyiannis DP (2003) Infections in patients with aplastic anemia: experience at a tertiary care cancer center. Cancer 98:86–93PubMedCrossRef Torres HA, Bodey GP, Rolston KV, Kantarjian HM, Raad II, Kontoyiannis DP (2003) Infections in patients with aplastic anemia: experience at a tertiary care cancer center. Cancer 98:86–93PubMedCrossRef
Zurück zum Zitat Yamato Y, Kaneko H, Hashimoto T et al (2002a) Pharmacokinetics of the antifungal drug micafungin in mice, rats and dogs, and its in vitro protein binding and distribution to blood cells. Jpn J Chemother 50:S74–S79 Yamato Y, Kaneko H, Hashimoto T et al (2002a) Pharmacokinetics of the antifungal drug micafungin in mice, rats and dogs, and its in vitro protein binding and distribution to blood cells. Jpn J Chemother 50:S74–S79
Zurück zum Zitat Yamato Y, Kaneko H, Yamasaki S et al (2002b) Distribution and excretion of intravenous dosing of [14C] micafungin to rats. Jpn J Chemother 50:S80–S87 Yamato Y, Kaneko H, Yamasaki S et al (2002b) Distribution and excretion of intravenous dosing of [14C] micafungin to rats. Jpn J Chemother 50:S80–S87
Metadaten
Titel
Effect of blood decrease on micafungin disposition in rats
verfasst von
Hiroki Konishi
Keizo Fukushima
Masatomo Sudo
Masaki Sumi
Tokuzo Minouchi
Ikumi Iga
Nobuhito Shibata
Akira Yamaji
Publikationsdatum
01.03.2011
Verlag
Springer-Verlag
Erschienen in
European Journal of Drug Metabolism and Pharmacokinetics / Ausgabe 1/2011
Print ISSN: 0378-7966
Elektronische ISSN: 2107-0180
DOI
https://doi.org/10.1007/s13318-011-0023-3

Weitere Artikel der Ausgabe 1/2011

European Journal of Drug Metabolism and Pharmacokinetics 1/2011 Zur Ausgabe