title: Pharmacokinetics of isoflavones from soy infant formula in neonatal and adult rhesus monkeys.
abstract: Consumption of soy infant formula represents a unique exposure scenario in which developing children ingest a mixture of endocrine-active isoflavones along with a substantial portion of daily nutrition. Genistein and daidzein were administered as glucoside conjugates to neonatal rhesus monkeys in a fortified commercial soy formula at 5, 35, and 70 days after birth. A single gavage dosing with 10 mg/kg bw genistein and 6 mg/kg bw daidzein was chosen to represent the upper range of typical daily consumption and to facilitate complete pharmacokinetic measurements for aglycone and total isoflavones and equol. Adult monkeys were also gavaged with the same formula solution at 2.8 and 1.6 mg/kg bw genistein and daidzein, respectively, and by IV injection with isoflavone aglycones (5.2 and 3.2 mg/kg bw, respectively) to determine absolute bioavailability. Significant differences in internal exposure were observed between neonatal and adult monkeys, with higher values for dose-adjusted AUC and Cmax of the active aglycone isoflavones in neonates. The magnitude and frequency of equol production by the gut microbiome were also significantly greater in adults. These findings are consistent with immaturity of metabolic and/or physiological systems in developing non-human primates that reduces total clearance of soy isoflavones from the body.
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA. Electronic address: daniel.doerge@fda.hhs.gov.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Doerge
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
authors.forename: Kellie A
authors.initials: KA
authors.lastname: Woodling
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
authors.forename: Mona I
authors.initials: MI
authors.lastname: Churchwell
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
authors.forename: Stefanie C
authors.initials: SC
authors.lastname: Fleck
authors.affiliation: Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, IL 61810, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Helferich
mesh_terms: D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D002853:Chromatography, Liquid; D006801:Humans; D007223:Infant; D041943:Infant Formula / Q000737:chemistry*; D007529:Isoflavones / Q000493:pharmacokinetics*; D008253:Macaca mulatta; D008297:Male; D030262:Soybean Proteins / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
chemical_list: D007529:Isoflavones; D030262:Soybean Proteins
keywords: Daidzein; Genistein; Mass spectrometry; Neonatal; Pharmacokinetics; Rhesus monkey; Soy