PMID- 25308868 OWN - NLM STAT- MEDLINE DCOM- 20151124 LR - 20221207 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 37 IP - 2 DP - 2015 Feb 1 TI - 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. PG - 302-10 LID - S0149-2918(14)00602-X [pii] LID - 10.1016/j.clinthera.2014.09.010 [doi] AB - PURPOSE: 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-infinity), t((1/2)), and T(max). Statistical analysis was performed for the assessment of dose proportionality. Tolerability was assessed for up to 96 hours after administration. FINDINGS: 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-infinity) 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-infinity) of amitriptyline hydrochloride 25 mg were 17.69 ng/mL, 260.68 ng.h/mL, and 296.87 ng.h/mL, respectively. IMPLICATIONS: 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. CI - Copyright (c) 2015 Elsevier HS Journals, Inc. All rights reserved. FAU - Nam, Yunsung AU - Nam Y AD - Department of Pharmacology, College of Medicine, Chung-ang University, Seoul, Republic of Korea. FAU - Lim, Cheol-Hee AU - Lim CH AD - Department of Pharmacology, College of Medicine, Chung-ang University, Seoul, Republic of Korea. FAU - Lee, Ho Sung AU - Lee HS AD - Department of Pharmacology, College of Medicine, Chung-ang University, Seoul, Republic of Korea. FAU - Chung, Su Jin AU - Chung SJ AD - Department of Pharmacology, College of Medicine, Chung-ang University, Seoul, Republic of Korea. FAU - Chung, Yoon Hee AU - Chung YH AD - Department of Anatomy, College of Medicine, Chung-ang University, Seoul, Republic of Korea. FAU - Shin, Yong Kyoo AU - Shin YK AD - Department of Pharmacology, College of Medicine, Chung-ang University, Seoul, Republic of Korea. FAU - Kim, Min-Gul AU - Kim MG AD - Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea. FAU - Sohn, Uy Dong AU - Sohn UD AD - Department of pharmacology, College of Pharmacy, Chung-ang University, Seoul, Republic of Korea. FAU - Kim, Hyoung-Chun AU - Kim HC AD - Neuropsychopharmacology & Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, Republic of Korea. FAU - Jeong, Ji Hoon AU - Jeong JH AD - Department of Pharmacology, College of Medicine, Chung-ang University, Seoul, Republic of Korea. Electronic address: jhjeong3@cau.ac.kr. LA - eng SI - ClinicalTrials.gov/NCT01367080 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20141011 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Antidepressive Agents, Tricyclic) RN - 0 (Tablets) RN - 1806D8D52K (Amitriptyline) SB - IM MH - Administration, Oral MH - Adult MH - Amitriptyline/administration & dosage/adverse effects/*pharmacokinetics MH - Antidepressive Agents, Tricyclic/administration & dosage/adverse effects/*pharmacokinetics MH - Area Under Curve MH - Asian People MH - Biological Availability MH - Chromatography, High Pressure Liquid MH - Cross-Over Studies MH - Fasting/metabolism MH - Healthy Volunteers MH - Humans MH - Male MH - Republic of Korea MH - Tablets MH - Tandem Mass Spectrometry MH - Young Adult OTO - NOTNLM OT - Etravil OT - amitriptyline hydrochloride OT - antidepressant OT - pharmacokinetic OT - proportionality EDAT- 2014/10/14 06:00 MHDA- 2015/12/15 06:00 CRDT- 2014/10/14 06:00 PHST- 2014/05/08 00:00 [received] PHST- 2014/08/21 00:00 [revised] PHST- 2014/09/06 00:00 [accepted] PHST- 2014/10/14 06:00 [entrez] PHST- 2014/10/14 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] AID - S0149-2918(14)00602-X [pii] AID - 10.1016/j.clinthera.2014.09.010 [doi] PST - ppublish SO - Clin Ther. 2015 Feb 1;37(2):302-10. doi: 10.1016/j.clinthera.2014.09.010. Epub 2014 Oct 11.