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Chain length of dietary alkylresorcinols affects their in vivo elimination kinetics in rats
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Farmakometri)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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2013 (English)In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 143, no 10, 1573-1578 p.Article in journal (Refereed) Published
Abstract [en]

Two phenolic acids, 3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)- propanoic acid (DHPPA), are the major metabolites of cereal alkylresorcinols (ARs). Like their precursors, AR metabolites have been suggested as biomarkers for intake of whole-grain wheat and rye and as such could aid the understanding of diet-disease associations. This study estimated and compared pharmacokinetic parameters of ARs and their metabolites in rats and investigated differences in metabolite formation after ingestion of different AR homologs. Rats were i.v. infused for 30 min with 2, 12, or 23 μmol/kg DHBA or DHPPA or orally given the same amounts of the AR homologs, C17:0 and C25:0. Repeated plasma samples, obtained from rats for 6 h (i.v.) or 36 h (oral), were simultaneously analyzed for ARs and their metabolites by GC-mass spectrometry. Pharmacokinetic parameters were estimated by population-based compartmental modeling and noncompartmental calculation. A 1-compartment model best described C25:0 pharmacokinetics, whereas C17:0 and AR metabolites best fitted 2-compartment models. Combined models for simultaneous prediction of AR and metabolite concentration were more complex, with less reliable estimates of pharmacokinetic parameters. Although the AUC of C17:0 was lower than that of C25:0 (P < 0.05), the total amount and composition of AR metabolites did not differ between rats given C17:0 or C25:0. The elimination half-life of ARs and their metabolites increased with length of the side chain (P-trend < 0.001) and ranged from 1.2 h (DHBA) to 8.8 h (C25:0). The formation of AR metabolites was slower than their elimination, indicating that the rate of AR metabolism and not excretion of DHBA and DHPPA determines their plasma concentrations in rats.

Place, publisher, year, edition, pages
2013. Vol. 143, no 10, 1573-1578 p.
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Medical and Health Sciences Agricultural Sciences
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URN: urn:nbn:se:uu:diva-212999DOI: 10.3945/jn.113.178392ISI: 000330331700006PubMedID: 23946349OAI: oai:DiVA.org:uu-212999DiVA: diva2:680159
Available from: 2013-12-17 Created: 2013-12-17 Last updated: 2017-12-06Bibliographically approved

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Marklund, MattiStrömberg, Eric AHooker, Andrew CHammarlund-Udenaes, Margareta

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Marklund, MattiStrömberg, Eric AHooker, Andrew CHammarlund-Udenaes, Margareta
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Clinical Nutrition and MetabolismDepartment of Pharmaceutical Biosciences
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