title: Single- and Multiple-Dose Milnacipran Pharmacokinetics in Healthy Han Chinese Volunteers.
abstract: The pharmacokinetics of milnacipran have been studied in Caucasian subjects but not in Chinese subjects.
  
  
  
  This single-center, open-label study evaluated the pharmacokinetics and safety of oral milnacipran administered as a randomized, three-way crossover, single-dose (25, 50 and 100 mg) and in multiple doses for 8 days (up to 100 mg/day administered as 50 mg twice daily) in Han Chinese healthy volunteers. Both the single- and multiple-dose studies included 12 different adults (six males and six females), respectively. Pharmacokinetic parameters for milnacipran were determined using WinNonlin version 6.3. The safety evaluation included adverse events (AEs) assessed by monitoring, physical examinations, vital signs, and clinical laboratory tests.
  
  
  
  Plasma concentrations of milnacipran reached a time to maximum concentration (t max) of 1.2-4.3 h after each single dose, and then declined, with a mean half-life (t ½) of 7.0-7.3 h over the dose range of 25-100 mg; the area under the curve (AUC) and maximum concentration (C max) values increased in a dose-proportional manner. After multiple doses, steady state was reached by day 4 and the accumulation was low, with an accumulation index <1.65. No significant sex differences were observed in milnacipran pharmacokinetic parameters and, additionally, no severe AEs were observed in the single- or multiple-dose studies. The most common reported AEs were nausea, vomiting, dizziness and water brash, which appears to be dose-related.
  
  
  
  Milnacipran was safe and well-tolerated in healthy volunteers and displayed linear increase in the C max and AUC values at doses ranging from 25 to 100 mg once daily.
authors.affiliation: Laboratory of Clinical Psychopharmacology, Beijing Key Lab of Mental Disorders, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Lane, Dewai Avenue, Xicheng District, 100088, Beijing, China.
authors.forename: Can-Jun
authors.initials: CJ
authors.lastname: Ruan
authors.affiliation: Laboratory of Clinical Psychopharmacology, Beijing Key Lab of Mental Disorders, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Lane, Dewai Avenue, Xicheng District, 100088, Beijing, China.
authors.forename: An-Ning
authors.initials: AN
authors.lastname: Li
authors.affiliation: Laboratory of Clinical Psychopharmacology, Beijing Key Lab of Mental Disorders, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Lane, Dewai Avenue, Xicheng District, 100088, Beijing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Dong
authors.affiliation: Laboratory of Clinical Psychopharmacology, Beijing Key Lab of Mental Disorders, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Lane, Dewai Avenue, Xicheng District, 100088, Beijing, China.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Zhai
authors.affiliation: Laboratory of Clinical Psychopharmacology, Beijing Key Lab of Mental Disorders, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Lane, Dewai Avenue, Xicheng District, 100088, Beijing, China.
authors.forename: Wen-Biao
authors.initials: WB
authors.lastname: Li
authors.affiliation: Laboratory of Clinical Psychopharmacology, Beijing Key Lab of Mental Disorders, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Lane, Dewai Avenue, Xicheng District, 100088, Beijing, China. wang.cy@163.net.
authors.forename: Chuan-Yue
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Mental Health Research Center at Eastern State Hospital, Lexington, KY, USA.|Psychiatry and Neurosciences Research Group (CTS-549), Institute of Neurosciences, University of Granada, Granada, Spain.|Biomedical Research Centre in Mental Health Net (CIBERSAM), Santiago Apóstol Hospital, University of the Basque Country, Vitoria, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: de Leon
mesh_terms: D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D018592:Cross-Over Studies; D003521:Cyclopropanes / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D000078764:Milnacipran; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D003521:Cyclopropanes; D000078764:Milnacipran