| Selective induction of propranolol metabolism by smoking: additional effects on renal clearance of metabolites. | |
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MedLine Citation:
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PMID: 3598909 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The objective of this study was to examine the effect of cigarette smoking on the activities of the three primary pathways governing propranolol metabolism in human subjects, i.e., glucuronidation, side-chain oxidation and ring oxidation. A single 80-mg dose of propranolol p.o. together with 40 muCi of 4-[3H]propranolol was given to six smoking and seven nonsmoking, young, white, male subjects and the oral clearance of propranolol and the partial clearances through these pathways were determined. The oral clearance of propranolol was increased by 77% (P less than .02) in smokers compared with nonsmokers. This apparent induction of propranolol metabolism was due to a 122% increase in side-chain oxidation (P less than .001) and a 55% increase in glucuronidation (P less than .01). There was no significant effect of smoking on aromatic ring oxidation. Smokers had a 30% greater renal clearance of total metabolites (P less than .05), due mainly to a 53% greater renal clearance of the acidic propranolol metabolite naphthoxylactic acid (P less than .001). These data show a selective effect of smoking on propranolol metabolism and suggest that side-chain oxidation and glucuronidation are mediated by isoenzymes inducible by aromatic hydrocarbons. The selective effect of smoking on the renal clearance of the major propranolol metabolite naphthoxylactic acid may be due to induction of a renal transport protein. |
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Authors:
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T Walle; U K Walle; T D Cowart; E C Conradi; T E Gaffney |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 241 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 1987 Jun |
Date Detail:
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Created Date: 1987-07-30 Completed Date: 1987-07-30 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 928-33 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Creatinine / metabolism Half-Life Humans Kidney / metabolism* Lactates / metabolism Male Metabolic Clearance Rate Propranolol / analogs & derivatives, metabolism* Smoking* |
| Grant Support | |
ID/Acronym/Agency:
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HL 29566/HL/NHLBI NIH HHS; RR 01070/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Lactates; 10476-54-7/naphthoxylactic acid; 525-66-6/Propranolol; 60-27-5/Creatinine; 66322-66-5/propranolol glucuronide; 94731-13-2/4-hydroxypropranolol glucuronide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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