![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Abstract
Nitrofurantoin is a commonly used urinary tract antibiotic prescribed to lactating woman. It is actively transported into human and rat milk by an unknown mechanism. Our group has demonstrated an important role of the breast cancer resistance protein (BCRP/ABCG2) in the secretion of xenotoxins into the milk. This ATP-binding cassette drug efflux transporter extrudes xenotoxins from cells in intestine, liver, mammary gland, and other organs, affecting the pharmacological and toxicological behavior of many compounds. We investigated whether Bcrp1 is involved in the pharmacokinetic profile of nitrofurantoin and its active secretion into the milk. Using polarized cell lines, we found that nitrofurantoin is efficiently transported by murine Bcrp1 and human BCRP. After oral administration of 10 mg/kg nitrofurantoin, the area under the plasma concentrationtime curve in Bcrp1 knockout mice was almost 4-fold higher than in wild-type mice (148.8 ± 30.4 versus 37.5 ± 6.8 min · µg/ml); and after i.v. administration (5 mg/kg), 2-fold higher (139.2 ± 22.0 versus 73.9 ± 9.0 min · µg/ml). Hepatobiliary excretion of nitrofurantoin was almost abolished in Bcrp1 knockout mice (9.6 ± 3.2 versus 0.2 ± 0.1% in wild-type and Bcrp1 knockout mice, respectively). The milk-to-plasma ratio of nitrofurantoin was almost 80 times higher in wild-type compared with Bcrp1 knockout lactating female mice (45.7 ± 16.2 versus 0.6 ± 0.1). Nitrofurantoin elimination via milk was quantitatively even higher than hepatobiliary elimination. We conclude that Bcrp1 is an important determinant for the bioavailability of nitrofurantoin and the main mechanism involved in its hepatobiliary excretion and secretion into the milk.
Address correspondence to: Dr. Alfred H. Schinkel, Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. E-mail: a.schinkel{at}nki.nl
This article has been cited by other articles:
|
|
 |
|
  K. He, M. W. Lago, R. A. Iyer, W.-C. Shyu, W. G. Humphreys, and L. J. Christopher Lacteal Secretion, Fetal and Maternal Tissue Distribution of Dasatinib in Rats Drug Metab. Dispos., December 1, 2008; 36(12): 2564 - 2570. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wang, M. Leggas, M. Goswami, P. E. Empey, and P. J. McNamara N-(4-[2-(1,2,3,4-Tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine Carboxamide (GF120918) As a Chemical ATP-Binding Cassette Transporter Family G Member 2 (Abcg2) Knockout Model to Study Nitrofurantoin Transfer into Milk Drug Metab. Dispos., December 1, 2008; 36(12): 2591 - 2596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Matsushima, K. Maeda, H. Hayashi, Y. Debori, A. H. Schinkel, J. D. Schuetz, H. Kusuhara, and Y. Sugiyama Involvement of Multiple Efflux Transporters in Hepatic Disposition of Fexofenadine Mol. Pharmacol., May 1, 2008; 73(5): 1474 - 1483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhou, S. B. Naraharisetti, H. Wang, J. D. Unadkat, M. F. Hebert, and Q. Mao The Breast Cancer Resistance Protein (Bcrp1/Abcg2) Limits Fetal Distribution of Glyburide in the Pregnant Mouse: An Obstetric-Fetal Pharmacology Research Unit Network and University of Washington Specialized Center of Research Study Mol. Pharmacol., March 1, 2008; 73(3): 949 - 959. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhang, H. Wang, J. D. Unadkat, and Q. Mao Breast Cancer Resistance Protein 1 Limits Fetal Distribution of Nitrofurantoin in the Pregnant Mouse Drug Metab. Dispos., December 1, 2007; 35(12): 2154 - 2158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Tian, J. Li, M. J. Zamek-Gliszczynski, A. S. Bridges, P. Zhang, N. J. Patel, T. J. Raub, G. M. Pollack, and K. L. R. Brouwer Roles of P-Glycoprotein, Bcrp, and Mrp2 in Biliary Excretion of Spiramycin in Mice Antimicrob. Agents Chemother., September 1, 2007; 51(9): 3230 - 3234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yamagata, H. Kusuhara, M. Morishita, K. Takayama, H. Benameur, and Y. Sugiyama Improvement of the Oral Drug Absorption of Topotecan through the Inhibition of Intestinal Xenobiotic Efflux Transporter, Breast Cancer Resistance Protein, by Excipients Drug Metab. Dispos., July 1, 2007; 35(7): 1142 - 1148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wang and M. E. Morris Effects of the Flavonoid Chrysin on Nitrofurantoin Pharmacokinetics in Rats: Potential Involvement of ABCG2 Drug Metab. Dispos., February 1, 2007; 35(2): 268 - 274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Enokizono, H. Kusuhara, and Y. Sugiyama Involvement of Breast Cancer Resistance Protein (BCRP/ABCG2) in the Biliary Excretion and Intestinal Efflux of Troglitazone Sulfate, the Major Metabolite of Troglitazone with a Cholestatic Effect Drug Metab. Dispos., February 1, 2007; 35(2): 209 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Sarkadi, L. Homolya, G. Szakacs, and A. Varadi Human Multidrug Resistance ABCB and ABCG Transporters: Participation in a Chemoimmunity Defense System. Physiol Rev, October 1, 2006; 86(4): 1179 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Choudhuri and C. D. Klaassen Structure, Function, Expression, Genomic Organization, and Single Nucleotide Polymorphisms of Human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) Efflux Transporters International Journal of Toxicology, July 1, 2006; 25(4): 231 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-i. Nezasa, X. Tian, M. J. Zamek-Gliszczynski, N. J. Patel, T. J. Raub, and K. L. R. Brouwer ALTERED HEPATOBILIARY DISPOSITION OF 5 (AND 6)-CARBOXY-2',7'-DICHLOROFLUORESCEIN IN Abcg2 (Bcrp1) AND Abcc2 (Mrp2) KNOCKOUT MICE Drug Metab. Dispos., April 1, 2006; 34(4): 718 - 723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Merino, A. I. Alvarez, M. M. Pulido, A. J. Molina, A. H. Schinkel, and J. G. Prieto BREAST CANCER RESISTANCE PROTEIN (BCRP/ABCG2) TRANSPORTS FLUOROQUINOLONE ANTIBIOTICS AND AFFECTS THEIR ORAL AVAILABILITY, PHARMACOKINETICS, AND MILK SECRETION Drug Metab. Dispos., April 1, 2006; 34(4): 690 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Kwok, A. Yamauchi, R. Rajesan, L. Chan, U. Dhillon, W. Gao, H. Xu, B. Wang, S. Takahashi, J. Semple, et al. Carnitine/xenobiotics transporters in the human mammary gland epithelia, MCF12A Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R793 - R802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Merino, A. E. van Herwaarden, E. Wagenaar, J. W. Jonker, and A. H. Schinkel Sex-Dependent Expression and Activity of the ATP-Binding Cassette Transporter Breast Cancer Resistance Protein (BCRP/ABCG2) in Liver Mol. Pharmacol., May 1, 2005; 67(5): 1765 - 1771. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
