Involvement of multidrug resistance-associated protein 2 (ABCC2/Mrp2) in biliary excretion of micafungin in rats

被引：11

作者：

Abe, Fumie ^{[1
]}

Ueyama, Jun ^{[2
]}

Kimata, Akiko ^{[2
]}

Kato, Miki ^{[1
]}

Hayashi, Tamon ^{[1
]}

Nadai, Masayuki ^{[3
]}

Saito, Hiroko ^{[1
]}

Takeyama, Naoshi ^{[4
]}

Noguchi, Hiroshi ^{[4
]}

Hasegawa, Takaaki ^{[1
]}

机构：

[1] Aichi Med Univ, Dept Pharm & Pharmacokinet, Sch Med, Nagakute, Aichi 4801195, Japan

[2] Nagoya Univ, Dept Med Technol, Sch Hlth Sci, Higashi Ku, Nagoya, Aichi 4618673, Japan

[3] Meijo Univ, Fac Pharmaceut Sci, Tenpaku Ku, Nagoya, Aichi 4688503, Japan

[4] Aichi Med Univ, Dept Crit Care Med, Sch Med, Nagakute, Aichi 4801195, Japan

来源：

LIFE SCIENCES | 2008年 / 83卷 / 7-8期

关键词：

micafungin; multidrug resistance-associated protein 2 (ABCC2/Mrp2) hepatobiliary excretion; Eisai hyperbilirubinemic rats (EHBR);

D O I：

10.1016/j.lfs.2008.06.013

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The drug transporter, multidrug resistance-associated protein 2 (ABCC2/Mrp2), is known to play important roles in excretion of various drugs. In the present study, we investigated whether Mrp2 is involved in the transport of micafungin, a newly developed antifungal agent. When Sprague-Dawley rats received an intravenous injection of micafungin (1 mg/kg) in combination with cyclosporine, the cyclosporine significantly delayed the disappearance of micafungin from plasma and decreased the systemic clearance and volume of distribution at steady-state of micafungin to 54% and 65% of the corresponding control values, respectively. When Sprague-Dawley rats received a constant-rate infusion of micafungin, cyclosporine significantly decreased the steady-state biliary clearance of micafungin (similar to 80%). A significant decrease in the biliary clearance of micafungin (similar to 60%) was observed in Eisai hyperbilirubinemic rats, which have a hereditary deficiency in Mrp2. The present findings at least suggest that Mrp2 is involved mainly in the hepatobiliary excretion of micafungin in rats. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：229 / 235

页数：7

共 28 条

[1] Sinusoidal efflux of taurocholate is enhanced in Mrp2-deficient rat liver [J].

Akita, H ;

Suzuki, H ;

Sugiyama, Y .

PHARMACEUTICAL RESEARCH, 2001, 18 (08) :1119-1125

[2] Azithromycin reverses anticancer drug resistance and modifies hepatobiliary excretion of doxorubicin in rats [J].

Asakura, E ;

Nakayama, H ;

Sugie, M ;

Zhao, YL ;

Nadai, M ;

Kitaichi, K ;

Shimizu, A ;

Miyoshi, M ;

Takagi, K ;

Hasegawa, T .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2004, 484 (2-3) :333-339

[3] The multidrug resistance protein family [J].

Borst, P ;

Evers, R ;

Kool, M ;

Wijnholds, J .

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1999, 1461 (02) :347-357

[4] Effect of multidrug resistance-reversing agents on transporting activity of human canalicular multispecific organic anion transporter [J].

Chen, ZS ;

Kawabe, T ;

Ono, M ;

Aoki, S ;

Sumizawa, T ;

Furukawa, T ;

Uchiumi, T ;

Wada, M ;

Kuwano, M ;

Akiyama, S .

MOLECULAR PHARMACOLOGY, 1999, 56 (06) :1219-1228

[5]

Gotoh Y, 2000, J PHARMACOL EXP THER, V292, P433

[6] Concomitant tacrolimus and micafungin pharmacokinetics in healthy volunteers [J].

Hebert, ME ;

Blough, DK ;

Townsend, RW ;

Allison, M ;

Buell, D ;

Keirns, J ;

Bekersky, I .

JOURNAL OF CLINICAL PHARMACOLOGY, 2005, 45 (09) :1018-1024

[7] Concomitant cyclosporine and micafungin pharmacokinetics in healthy volunteers [J].

Hebert, ME ;

Townsend, RW ;

Austin, S ;

Balan, G ;

Blough, DK ;

Buell, D ;

Keirns, J ;

Bekersky, I .

JOURNAL OF CLINICAL PHARMACOLOGY, 2005, 45 (08) :954-960

[8] Shiga-like toxin II impairs hepatobiliary transport of doxorubicin in rats by down-regulation of hepatic P glycoprotein and multidrug resistance-associated protein Mrp2 [J].

Hidemura, K ;

Zhao, YL ;

Ito, K ;

Nakao, A ;

Tatsumi, Y ;

Kanazawa, H ;

Takagi, K ;

Ohta, M ;

Hasegawa, T .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2003, 47 (05) :1636-1642

[9]

Hirohashi T, 1998, MOL PHARMACOL, V53, P1068

[10]

KANEKO H, 2002, JPN J CHEMOTHER S1, V50, P88

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