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Knud Erik Bach Knudsen

Simultaneous Pharmacokinetic Modeling of Alkylresorcinols and Their Main Metabolites Indicates Dual Absorption Mechanisms and Enterohepatic Elimination in Humans

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Matti Marklund, Ukendt
  • Eric A, Strömberg, Sveriges Lantbrugsuniversitet, Uppsala, Sverige
  • Helle Nygaard Lærke
  • Knud Erik Bach Knudsen
  • Afaf Kamal-Eldin, Danmark
  • Andrew C. Hooker, Sverige
  • Rikard Landberg, Department of Food Science, BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden., Danmark
Alkylresorcinols have proven to be useful biomarkers of whole-grain wheat and rye intake in many nutritional studies. To improve their utility, more knowledge regarding the fate of alkylresorcinols and their metabolites after consumption is needed.Objective: The objective of this study was to develop a combined pharmacokinetic model for plasma concentrations of alkylresorcinols and their 2 major metabolites, 3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-propanoic acid (DHPPA).Methods: The model was established by using plasma samples collected from 3 women and 2 men after a single dose (120 g) of rye bran and validated against fasting plasma concentrations from 8 women and 7 men with controlled rye bran intake (23, 45, or 90 g/d). Alkylresorcinols in the lymph and plasma of a pig fed a single alkylresorcinol dose (1.3 mmol) were quantified to assess absorption. Human ileostomal effluent and pig bile after high and low alkylresorcinol doses were analyzed to evaluate biliary alkylresorcinol metabolite excretion.Results: The model contained 2 absorption compartments: 1 that transferred alkylresorcinols directly to the systematic circulation and 1 in which a proportion of absorbed alkylresorcinols was metabolized before reaching the systemic circulation. Plasma concentrations of alkylresorcinols and their metabolites depended on absorption and formation, respectively, and the mean ± SEM terminal elimination half-life of alkylresorcinols (1.9 ± 0.59 h), DHPPA (1.5 ± 0.26 h), and DHBA (1.3 ± 0.22 h) did not differ. The model accurately predicted alkylresorcinol and DHBA concentrations after repeated alkylresorcinol intake but DHPPA concentration was overpredicted, possibly because of poorly modeled enterohepatic circulation. During the 8 h following administration, <2% of the alkylresorcinol dose was recovered in the lymph. DHPPA was identified in both human ileostomal effluent and pig bile, indicating availability of DHPPA for absorption and enterohepatic circulation.Conclusion: Intact alkylresorcinols have advantages over DHBA and DHPPA as plasma biomarkers for whole-grain wheat and rye intake because of lower susceptibility to factors other than alkylresorcinol intake.
OriginalsprogEngelsk
TidsskriftJournal of Nutrition
Vol/bind144
Nummer1
Sider (fra-til)1674-1680
Antal sider7
ISSN0022-3166
DOI
StatusUdgivet - 1 nov. 2014

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