title: Single-dose, randomized, open-label, 2-way crossover study of the pharmacokinetics of amitriptyline hydrochloride 10- and 25-mg tablet in healthy male Korean volunteers.
abstract: OBJECTIVE
  Amitriptyline is the most widely used tricyclic antidepressant (TCA). Although amitriptyline hydrochloride 10 and 25 mg has been marketed in Korea, no data on the dose proportionality of amitriptyline in Korean subjects are available. This clinical trial was designed to evaluate and compare the relative bioavailability with regard to dose proportionality between the two marketed strengths of amitriptyline hydrochloride tablets after a single-dose, oral administration under fasting conditions in healthy, male, Korean volunteers.
  
  
  METHODS
  This single-dose, randomized, open-label, 2-way crossover study was conducted in healthy male Korean subjects. Subjects were randomly assigned to 1 of 2 dose groups and received a single dose of 10 or 25 mg amitriptyline hydrochloride under fasting conditions, followed by the alternate dose in the subsequent study period. High performance liquid chromatography (HPLC)-mass spectrometry (MS)/MS detection was applied to determine plasma concentrations. Pharmacokinetic parameters were calculated, C(max), AUC(last), AUC(0-∞), t(½), and T(max). Statistical analysis was performed for the assessment of dose proportionality. Tolerability was assessed for up to 96 hours after administration.
  
  
  RESULTS
  Twelve healthy Korean subjects completed this trial (mean [SD] age, 21.7 [1.9] years; height, 174.5 [5.0] cm; and weight, 66.7 [9.4] kg). Although 4 subjects experienced a total 5 adverse events (AEs), no serious AEs were reported during the study. The mean values of C(max) and AUC were proportional to the doses of 10 and 25 mg. The C(max), AUC(last), and AUC(0-∞) of amitriptyline hydrochloride 10 mg were 5.96 ng/mL, 91.35 ng·h/mL and 109.74 ng·h/mL, respectively. The C(max), AUC(last), and AUC(0-∞) of amitriptyline hydrochloride 25 mg were 17.69 ng/mL, 260.68 ng·h/mL, and 296.87 ng·h/mL, respectively.
  
  
  CONCLUSIONS
  Our results suggest that the 2 strengths of amitriptyline hydrochloride (10 and 25 mg) exhibited linear (dose-dependent) pharmacokinetics in these healthy, male, Korean subjects. Based on these results, a predictable and linear increase in systemic exposure can be expected. ClinicalTrials.gov identifier: NCT01367080.
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-ang University, Seoul, Republic of Korea.
authors.forename: Yunsung
authors.initials: Y
authors.lastname: Nam
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-ang University, Seoul, Republic of Korea.
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Lim
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-ang University, Seoul, Republic of Korea.
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-ang University, Seoul, Republic of Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Chung
authors.affiliation: Department of Anatomy, College of Medicine, Chung-ang University, Seoul, Republic of Korea.
authors.forename: Yoon Hee
authors.initials: YH
authors.lastname: Chung
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-ang University, Seoul, Republic of Korea.
authors.forename: Yong Kyoo
authors.initials: YK
authors.lastname: Shin
authors.affiliation: Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors.forename: Min-Gul
authors.initials: MG
authors.lastname: Kim
authors.affiliation: Department of pharmacology, College of Pharmacy, Chung-ang University, Seoul, Republic of Korea.
authors.forename: Uy Dong
authors.initials: UD
authors.lastname: Sohn
authors.affiliation: Neuropsychopharmacology & Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, Republic of Korea.
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-ang University, Seoul, Republic of Korea. Electronic address: jhjeong3@cau.ac.kr.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jeong
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000639:Amitriptyline / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005215:Fasting / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D056910:Republic of Korea; D013607:Tablets; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D000929:Antidepressive Agents, Tricyclic; D013607:Tablets; D000639:Amitriptyline
keywords: Etravil; amitriptyline hydrochloride; antidepressant; pharmacokinetic; proportionality