Tubular transport mechanisms of quinapril and quinaprilat in the isolated perfused rat kidney: Effect of organic anions and cations
dc.contributor.author | Olson, Stephen C. | en_US |
dc.contributor.author | Kugler, Alan R. | en_US |
dc.contributor.author | Smith, David E. | en_US |
dc.date.accessioned | 2006-09-11T15:37:01Z | |
dc.date.available | 2006-09-11T15:37:01Z | |
dc.date.issued | 1996-08 | en_US |
dc.identifier.citation | Kugler, Alan R.; Olson, Stephen C.; Smith, David E.; (1996). "Tubular transport mechanisms of quinapril and quinaprilat in the isolated perfused rat kidney: Effect of organic anions and cations." Journal of Pharmacokinetics and Biopharmaceutics 24(4): 349-368. <http://hdl.handle.net/2027.42/45053> | en_US |
dc.identifier.issn | 0090-466X | en_US |
dc.identifier.issn | 1573-8744 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/45053 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=9044165&dopt=citation | en_US |
dc.description.abstract | The clearance mechanisms of quinapril and quinaprilat were probed using an isolated perfused rat kidney model. Sixty-four experiments were performed with drug in the absence and presence of classic inhibitors of the organic acid (i.e., probenecid and p-aminohippurate) and organic base (i.e., tetraethylammonium and quinine) transport systems of the proximal tubule. Initial perfusate concentrations of quinapril and quinaprilat were approximately 2.36 μM (or 1000 ng/ml), and transport inhibitors were coperfused at 100–10,000 times the drugs' initial μM concentrations. Quinapril and quinaprilat concentrations were determined in perfusate, urine, and perfusate ultrafiltrate using a reversed-phase HPLC procedure with radiochemical detection, coupled to liquid scintillation spectrometry. Perfusate protein binding was determined using an ultrafiltration method at 37°C. Overall, the clearance ratios of quinapril (total renal clearance divided by fu·GFR ) and quinaprilat (urinary clearance divided by fu·GFR ) were significantly reduced, and in a dose-dependent manner, by the coperfusion of organic acids but not organic bases. The data demonstrate that the organic anionic secretory system is the primary mechanism by which quinapril and quinaprilat are transported into and across renal proximal cells. | en_US |
dc.format.extent | 992118 bytes | |
dc.format.extent | 3115 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Kluwer Academic Publishers-Plenum Publishers; Plenum Publishing Corporation ; Springer Science+Business Media | en_US |
dc.subject.other | Biomedical Engineering | en_US |
dc.subject.other | Transport | en_US |
dc.subject.other | Quinaprilat | en_US |
dc.subject.other | Organic Anions | en_US |
dc.subject.other | Veterinary Medicine | en_US |
dc.subject.other | Pharmacology/Toxicology | en_US |
dc.subject.other | Biomedicine | en_US |
dc.subject.other | Pharmacy | en_US |
dc.subject.other | Biochemistry, General | en_US |
dc.subject.other | Quinapril | en_US |
dc.subject.other | Isolated Perfused Rat Kidney | en_US |
dc.subject.other | Organic Cations | en_US |
dc.subject.other | Metabolism | en_US |
dc.title | Tubular transport mechanisms of quinapril and quinaprilat in the isolated perfused rat kidney: Effect of organic anions and cations | en_US |
dc.type | Article | 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 | Department of Pharmacokinetics and Drug Metabolism, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, 48106-1047, Ann Arbor, Michigan; College of Pharmacy and Upjohn Center for Clinical Pharmacology, 3705 Upjohn Center, The University of Michigan, 48109-0504, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | College of Pharmacy and Upjohn Center for Clinical Pharmacology, 3705 Upjohn Center, The University of Michigan, 48109-0504, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationother | Department of Pharmacokinetics and Drug Metabolism, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, 48106-1047, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationumcampus | Ann Arbor | en_US |
dc.identifier.pmid | 9044165 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/45053/1/10928_2006_Article_BF02353517.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1007/BF02353517 | en_US |
dc.identifier.source | Journal of Pharmacokinetics and Biopharmaceutics | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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