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
收藏
页码：229 / 235
页数：7
相关论文
共 50 条
  • [21] Functional analysis of dog multidrug resistance-associated protein 2 (Mrp2) in comparison with rat Mrp2
    Ninomiya, M
    Ito, K
    Horie, T
    DRUG METABOLISM AND DISPOSITION, 2005, 33 (02) : 225 - 232
  • [22] Single nucleotide polymorphisms in multidrug resistance associated protein 2 (MRP2/ABCC2): its impact on drug disposition
    Suzuki, H
    Sugiyama, Y
    ADVANCED DRUG DELIVERY REVIEWS, 2002, 54 (10) : 1311 - 1331
  • [23] LPS-induced dissociation of multidrug resistance-associated protein 2 (Mrp2) and radixin is associated with Mrp2 selective internalization in rats
    Saeki, Junjiro
    Sekine, Shuichi
    Horie, Toshiharu
    BIOCHEMICAL PHARMACOLOGY, 2011, 81 (01) : 178 - 184
  • [24] Quantitative immunofluorescent blotting of the Multidrug Resistance-associated Protein 2 (MRP2)
    Gerk, Phillip M.
    JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS, 2011, 63 (03) : 279 - 282
  • [25] Interaction of progestins with the human multidrug resistance-associated protein 2 (MRP2)
    Lindenmaier, H
    Becker, M
    Haefeli, WE
    Weiss, J
    DRUG METABOLISM AND DISPOSITION, 2005, 33 (11) : 1576 - 1579
  • [26] Regulation of multidrug resistance protein 2 (MRP2, ABCC2) expression by statins: Involvement of SREBP-mediated gene regulation
    Kobayashi, Masaki
    Gouda, Keisuke
    Chisaki, Ikumi
    Asada, Koji
    Ogura, Jiro
    Takahashi, Natsuko
    Konishi, Toru
    Koshida, Yusuke
    Sasaki, Shotaro
    Yamaguchi, Hiroaki
    Iseki, Ken
    INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2013, 452 (1-2) : 36 - 41
  • [27] Novel mutations identified in the human multidrug resistance-associated protein 2 (MRP2/ABCC2) gene in a Japanese patient with Dubin-Johnson syndrome
    Shoda, J
    Suzuki, H
    Suzuki, H
    Sugiyama, Y
    Hirouchi, M
    Utsunomiya, H
    Oda, K
    Kawamoto, T
    Matsuzaki, Y
    Tanaka, N
    HEPATOLOGY RESEARCH, 2003, 27 (04) : 322 - 325
  • [28] The effects of multidrug resistance protein 2 (Mrp2) and breast cancer resistance protein (Bcrp) on biliary excretion of cefditoren in rats
    MENG QiangLIU QiWANG ChangyuanLIU KexinDalian Medical UniversityDalian China
    沈阳药科大学学报, 2008, 25(S1) (S1) : 79 - 80
  • [29] Hepatic Metabolism and Biliary Excretion of Silymarin Flavonolignans in Isolated Perfused Rat Livers: Role of Multidrug Resistance-Associated Protein 2 (Abcc2)
    Miranda, Sonia R.
    Lee, Jin Kyung
    Brouwer, Kim L. R.
    Wen, Zhiming
    Smith, Philip C.
    Hawke, Roy L.
    DRUG METABOLISM AND DISPOSITION, 2008, 36 (11) : 2219 - 2226
  • [30] Noncholestatic estrogen glucuronides interact with the multidrug resistance-associated protein 2 (Mrp2)
    Gerk, PM
    Li, W
    Vore, M
    FASEB JOURNAL, 2003, 17 (05): : A1027 - A1027
12345