TY - JOUR
T1 - Chain length of dietary alkylresorcinols affects their in vivo elimination kinetics in rats1-3
AU - Marklund, Matti
AU - Strömberg, Eric A.
AU - Hooker, Andrew C.
AU - Hammarlund-Udenaes, Margareta
AU - Åman, Per
AU - Landberg, Rikard
AU - Kamal-Eldin, Afaf
PY - 2013
Y1 - 2013
N2 - 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 couldaid 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 mmol/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.) or36 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.
AB - 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 couldaid 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 mmol/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.) or36 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.
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U2 - 10.3945/jn.113.178392
DO - 10.3945/jn.113.178392
M3 - Article
C2 - 23946349
AN - SCOPUS:84885801997
SN - 0022-3166
VL - 143
SP - 1573
EP - 1578
JO - Journal of Nutrition
JF - Journal of Nutrition
IS - 10
ER -