| Effect of organ perfusion on renal drug transport. Application to furosemide in the isolated perfused rat kidney. | |
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MedLine Citation:
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PMID: 2566466 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Angiotensin II was used as a probe to study the effect of changes in perfusate flow rate on the renal clearance parameters of furosemide in the isolated perfused rat kidney. Drug studies were performed in three rats with no angiotensin II present in the perfusate (treatment I) and in three rats with a 2.7 ng/min infusion of angiotensin II into the perfusate (treatment II). Furosemide was introduced into the recirculating perfusate at an initial concentration of 3.5 micrograms/ml and was assayed using HPLC. The protein binding of furosemide in perfusate was determined by equilibrium dialysis. Angiotensin II was found to have a dramatic effect on the renal hemodynamics, resulting in a 42% decrease in perfusate flow, a 27% decrease in GFR, and a 25% increase in filtration fraction. Values for the fractional excretion of glucose were very low and consistent, with or without angiotensin II (3.0-3.5%). Although the fraction unbound of furosemide was unchanged between treatments (0.770 for treatment I vs. 0.695% for treatment II), the renal and secretion clearances of furosemide were reduced by about 30% in the presence of angiotensin II. However, if the renal clearance (CLr) was corrected for free fraction (fu) and glomerular filtration rate (GFR) [ER = CLr/(fu.GFR)], there was no difference between the excretion ratio (ER) values of furosemide after the two treatments (29.0 for treatment I vs. 29.6 for treatment II). These results imply that the altered clearance parameters of furosemide are more likely the consequence of a reduction in functional nephron mass rather than a change in intrinsic secretory transport per unit mass of nephron. |
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Authors:
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L J Lee; D E Smith |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Drug metabolism and disposition: the biological fate of chemicals Volume: 17 ISSN: 0090-9556 ISO Abbreviation: Drug Metab. Dispos. Publication Date: 1989 Jan-Feb |
Date Detail:
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Created Date: 1989-07-05 Completed Date: 1989-07-05 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9421550 Medline TA: Drug Metab Dispos Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 32-6 Citation Subset: IM |
Affiliation:
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College of Pharmacy, University of Michigan, Ann Arbor 48109-1065. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II
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pharmacology Animals Biological Transport Furosemide / metabolism* Glomerular Filtration Rate / drug effects Kidney / metabolism* Male Perfusion Rats Rats, Inbred Strains |
| Grant Support | |
ID/Acronym/Agency:
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GM 35498/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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11128-99-7/Angiotensin II; 54-31-9/Furosemide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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