Disposition of WR-1065 in the liver of tumor-bearing rats following regional vs systemic administration of amifostine
dc.contributor.author | Levi, Micha | en_US |
dc.contributor.author | DeRemer, Susan J. | en_US |
dc.contributor.author | Dou, Chunzhi | en_US |
dc.contributor.author | Ensminger, William D. | en_US |
dc.contributor.author | Smith, David E. | en_US |
dc.date.accessioned | 2006-04-19T13:41:52Z | |
dc.date.available | 2006-04-19T13:41:52Z | |
dc.date.issued | 2004-01 | en_US |
dc.identifier.citation | Levi, Micha; DeRemer, Susan J.; Dou, Chunzhi; Ensminger, William D.; Smith, David E. (2004)."Disposition of WR-1065 in the liver of tumor-bearing rats following regional vs systemic administration of amifostine." Biopharmaceutics & Drug Disposition 25(1): 27-35. <http://hdl.handle.net/2027.42/34602> | en_US |
dc.identifier.issn | 0142-2782 | en_US |
dc.identifier.issn | 1099-081X | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/34602 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=14716750&dopt=citation | en_US |
dc.description.abstract | Purpose —Amifostine is a prodrug in which selectivity is largely determined by the preferential formation and uptake of its cytoprotective metabolite, WR-1065, in normal tissues as a result of differences in membrane-bound alkaline phosphatase activity. It was hypothesized that amifostine may be a good candidate for regional drug delivery to the liver because of its large hepatic extraction and total body clearance. Methods —Rat livers were implanted with Walker-256 tumors. The tumor-bearing rats received 15 min infusions of amifostine (200 mg/kg) via the portal vein or the femoral vein. WR-1065 concentrations in the blood, liver and tumor were measured at various times. Results —The WR-1065 tumor portal dosing AUC 15−60 was 40% of systemic dosing, and tumor concentrations following portal dosing were one-fifth of that following systemic dosing. The portal dosing WR-1065 liver AUC 15−60 was 60% higher than the values for systemic dosing. The liver/tumor concentration ratios of WR-1065 following portal dosing were up to 8-fold higher than the ratio following systemic administration. Unfortunately, systemic exposure to WR-1065 was greater following portal vs systemic amifostine. Conclusions —Amifostine may provide increased liver protection and decreased tumor protection from radio- or chemotherapy when administered by the portal vein. However, portal dosing also increases systemic exposure to WR-1065, which is associated with hypotension. Copyright © 2004 John Wiley & Sons, Ltd. | en_US |
dc.format.extent | 144722 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | John Wiley & Sons, Ltd. | en_US |
dc.subject.other | Chemistry | en_US |
dc.subject.other | Food Science, Agricultural, Medicinal and Pharmaceutical Chemistry | en_US |
dc.title | Disposition of WR-1065 in the liver of tumor-bearing rats following regional vs systemic administration of amifostine | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Pharmacy and Pharmacology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | College of Pharmacy, The University of Michigan, Ann Arbor, Michigan, USA ; Upjohn Center for Clinical Pharmacology, The University of Michigan, Ann Arbor, Michigan, USA ; Box 0626, University of California, San Francisco, CA 94143-0626, USA | en_US |
dc.contributor.affiliationum | Upjohn Center for Clinical Pharmacology, The University of Michigan, Ann Arbor, Michigan, USA | en_US |
dc.contributor.affiliationum | Upjohn Center for Clinical Pharmacology, The University of Michigan, Ann Arbor, Michigan, USA | en_US |
dc.contributor.affiliationum | Upjohn Center for Clinical Pharmacology, The University of Michigan, Ann Arbor, Michigan, USA ; Department of Pharmacology and Internal Medicine, The University of Michigan, Ann Arbor, Michigan, USA | en_US |
dc.contributor.affiliationum | College of Pharmacy, The University of Michigan, Ann Arbor, Michigan, USA ; Upjohn Center for Clinical Pharmacology, The University of Michigan, Ann Arbor, Michigan, USA | en_US |
dc.identifier.pmid | 14716750 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/34602/1/380_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/bdd.380 | en_US |
dc.identifier.source | Biopharmaceutics & Drug Disposition | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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