title: Multiple-Ascending-Dose Pharmacokinetics and Safety Evaluation of Baicalein Chewable Tablets in Healthy Chinese Volunteers.
abstract: OBJECTIVE
  Baicalein, a flavonoid isolated from the root of Scutellaria baicalensis Georgi, is a neuroprotective agent under development to treat Parkinson's disease. This study investigated the pharmacokinetics, safety and tolerability of baicalein after a multiple-ascending-dose protocol in healthy Chinese volunteers.
  
  
  METHODS
  In this single-center, double-blind, placebo-controlled, parallel-group study, participants were randomized to receive baicalein (n = 8 per dose regimen) or placebo (n = 2 per dose regimen). Dosing regimens were 200, 400, and 800 mg once daily on days 1 and 10, twice daily on days 3-9. Plasma, urine, and feces samples were assayed for baicalein and its predominant metabolite baicalin using validated HPLC-MS/MS methods. Pharmacokinetic parameters were computed using standard non-compartmental analysis. Dose proportionality was assessed with a method combining equivalence criterion and power model. Drug safety and tolerability were assessed by monitoring adverse events and laboratory parameters.
  
  
  RESULTS
  Thirty-three of 36 enrolled participants completed the study. A total of 44 adverse events occurred in 23 participants. A steady-state concentration of analytes in plasma was achieved on day 8 after repeated dosing. Analytes concentrations and exposure increased with increasing dose. The dose proportionality constant (β) for AUCss of baicalein and baicalin was 0.922 (90 % confidence interval, 0.650-1.195) and 0.942 (90 % confidence interval, 0.539-1.345), respectively. The accumulation index varied from 1.66 to 2.07 for baicalein and from 1.68 to 2.45 for baicalin.
  
  
  CONCLUSIONS
  In dose range of 200-800 mg, multiple-dose oral baicalein administration was safe and well tolerated, dose proportionality was inconclusive, and no serious accumulation of baicalein was observed.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People's Republic of China.|Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Pharmacy, Beijing Hospital, No.1 Dahua Road, Beijing, 100730, People's Republic of China.
authors.forename: Hongxian
authors.initials: H
authors.lastname: Pang
authors.affiliation: Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Pharmacy, Beijing Hospital, No.1 Dahua Road, Beijing, 100730, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xue
authors.affiliation: Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Pharmacy, Beijing Hospital, No.1 Dahua Road, Beijing, 100730, People's Republic of China. aixins0302@126.com.
authors.forename: Aixin
authors.initials: A
authors.lastname: Shi
authors.affiliation: Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Pharmacy, Beijing Hospital, No.1 Dahua Road, Beijing, 100730, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Pharmacy, Beijing Hospital, No.1 Dahua Road, Beijing, 100730, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Pharmacy, Beijing Hospital, No.1 Dahua Road, Beijing, 100730, People's Republic of China.
authors.forename: Guoying
authors.initials: G
authors.lastname: Cao
authors.affiliation: Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Pharmacy, Beijing Hospital, No.1 Dahua Road, Beijing, 100730, People's Republic of China.
authors.forename: Bei
authors.initials: B
authors.lastname: Yan
authors.affiliation: Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Pharmacy, Beijing Hospital, No.1 Dahua Road, Beijing, 100730, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Dong
authors.affiliation: State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Pharmaceutical CO.LTD, Jiangsu, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Guorong
authors.initials: G
authors.lastname: He
authors.affiliation: Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Guanhua
authors.initials: G
authors.lastname: Du
authors.affiliation: Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Pharmacy, Beijing Hospital, No.1 Dahua Road, Beijing, 100730, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People's Republic of China. chenggang63@hotmail.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D044950:Flavanones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013607:Tablets; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D044950:Flavanones; D018696:Neuroprotective Agents; D013607:Tablets; C006680:baicalein