title: Single oral dose pharmacokinetics of decursin and decursinol angelate in healthy adult men and women.
abstract: The ethanol extract of Angelica gigas Nakai (AGN) root has promising anti-cancer and other bioactivities in rodent models. It is currently believed that the pyranocoumarin isomers decursin (D) and decursinol angelate (DA) contribute to these activities. We and others have documented that D and DA were rapidly converted to decursinol (DOH) in rodents. However, our in vitro metabolism studies suggested that D and DA might be metabolized differently in humans. To test this hypothesis and address a key question for human translatability of animal model studies of D and DA or AGN extract, we conducted a single oral dose human pharmacokinetic study of D and DA delivered through an AGN-based dietary supplement Cogni.Q (purchased from Quality of Life Labs, Purchase, NY) in twenty healthy subjects, i.e., 10 men and 10 women, each consuming 119 mg D and 77 mg DA from 4 vegicaps. Analyses of plasma samples using UHPLC-MS/MS showed mean time to peak concentration (Tmax) of 2.1, 2.4 and 3.3 h and mean peak concentration (Cmax) of 5.3, 48.1 and 2,480 nmol/L for D, DA and DOH, respectively. The terminal elimination half-life (t1/2) for D and DA was similar (17.4 and 19.3 h) and each was much longer than that of DOH (7.4 h). The mean area under the curve (AUC0-48h) for D, DA and DOH was estimated as 37, 335 and 27,579 h∙nmol/L, respectively. Gender-wise, men absorbed the parent compounds faster and took shorter time to reach DOH peak concentration. The human data supported an extensive conversion of D and DA to DOH, even though they metabolized DA slightly slower than rodents. Therefore, the data generated in rodent models concerning anti-cancer efficacy, safety, tissue distribution and pharmacodynamic biomarkers will likely be relevant for human translation.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02114957.
authors.affiliation: Department of Biomedical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, Texas, United States of America.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, Texas, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Clinical Research Unit, School of Medicine, Texas Tech University Health Sciences Center, Amarillo, Texas, United States of America.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Hale
authors.affiliation: Department of Biomedical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, Texas, United States of America.
authors.forename: Wayne
authors.initials: W
authors.lastname: Chee
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Chengguo
authors.initials: C
authors.lastname: Xing
authors.affiliation: Department of Biomedical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, Texas, United States of America.
authors.forename: Cheng
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Biomedical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, Texas, United States of America.
authors.forename: Junxuan
authors.initials: J
authors.lastname: Lü
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001578:Benzopyrans / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002087:Butyrates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D011788:Quality of Life; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D001578:Benzopyrans; D002087:Butyrates; C101278:decursin