PMID- 19393851
OWN - NLM
STAT- MEDLINE
DCOM- 20090611
LR  - 20221207
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 31
IP  - 3
DP  - 2009 Mar
TI  - An open-label, single-dose, parallel-group, dose-increasing study comparing the 
      pharmacokinetics and tolerability of pilsicainide hydrochloride in healthy Korean 
      and Japanese male subjects.
PG  - 609-18
LID - 10.1016/j.clinthera.2009.03.015 [doi]
AB  - BACKGROUND: Pilsicainide hydrochloride is a class IC antiarrhythmic agent used 
      for the treatment of supraventricular and ventricular arrhythmias. OBJECTIVE: The 
      objective of this study was to compare the pharmacokinetics and tolerability of 
      pilsicainide in healthy Korean and Japanese male volunteers to satisfy regulatory 
      requirements for marketing pilsicainide in the Republic of Korea. METHODS: This 
      was an open-label, single-dose, parallel-group, dose-increasing study. It was 
      simultaneously conducted in healthy Korean and Japanese volunteers from September 
      2005 through May 2006; pilsicainide was approved for use in the Republic of Korea 
      in 2007. Subjects for the 100-mg group were enrolled after the performance of 
      tolerability evaluations in the 50-mg dose group. Serial blood and urine samples 
      were collected up to 24 hours after dosing, and drug concentrations in plasma and 
      urine were determined by high-performance liquid chromatography. Tolerability was 
      evaluated by monitoring adverse events (AEs), clinical laboratory parameters, and 
      results of 12-lead electrocardiograms (ECGs). RESULTS: Sixteen healthy Korean 
      male subjects (mean [SD] age, 24.5 [4.2] years; weight, 71.8 [5.5] kg; height, 
      176.6 [6.3] cm) and 16 healthy male Japanese subjects (age, 24.7 [4.9] years; 
      weight, 60.2 [4.4] kg; height, 171.9 [6.4] cm) were enrolled in the study. Values 
      for AUC and C(max) of pilsicainide increased proportionally with dose escalation 
      in all subjects. Pilsicainide reached C(max) 0.5 to 1.5 hours after dosing in 
      both the Korean and Japanese subjects. The mean (SD) dose-normalized values for 
      C(max) for the Korean and Japanese subjects were 9.4 (1.9) and 9.2 (1.6) 
      ng/mL/mg, respectively. The mean (SD) dose-normalized values for AUC(0-infinity) 
      were 56.0 (8.0) ng . h/mL/mg in the Korean subjects and 53.8 (8.1) ng . h/mL/mg 
      in the Japanese subjects. None of these findings were statistically significant. 
      A total of 9 AEs occurred in 7 of the 16 Korean subjects; they included 
      dizziness, feeling of being hot, somnolence, and atrioventricular block. All of 
      the AEs were mild in severity and were considered possibly related to 
      pilsicainide. Two of the 16 Japanese subjects had a total of 4 AEs. All of the 
      AEs occurred in the subjects treated with 50 mg. Of the 2 subjects with AEs, 1 
      subject had a decrease in blood pressure, a sense of discomfort, and PR-interval 
      prolongation on ECG, while the other developed a premature ventricular 
      contraction (PVC). The PR-interval prolongation and PVC were determined to be 
      possibly related to pilsicainide, and these were mild in severity. The other AEs 
      (ie, decreased blood pressure, sense of discomfort) were moderate in severity. 
      CONCLUSIONS: The results of this study suggest that the pharmacokinetic profile 
      of pilsicainide was not significantly different between these healthy Korean and 
      Japanese male volunteers. A single dose (50 or 100 mg) of pilsicainide was well 
      tolerated in both ethnic groups.
FAU - Kim, Bo-Hyung
AU  - Kim BH
AD  - Department of Pharmacology and Clinical Pharmacology, Seoul National University 
      College of Medicine and Hospital, Jongno-gu, Seoul, Republic of Korea.
FAU - Kim, Jung-Ryul
AU  - Kim JR
FAU - Lim, Kyoung Soo
AU  - Lim KS
FAU - Kim, Jae Woo
AU  - Kim JW
FAU - Kim, Kyu-pyo
AU  - Kim KP
FAU - Hong, Jang-Hee
AU  - Hong JH
FAU - Jang, In-Jin
AU  - Jang IJ
FAU - Shin, Sang-Goo
AU  - Shin SG
FAU - Yu, Kyung-Sang
AU  - Yu KS
FAU - Tanaka, Takanori
AU  - Tanaka T
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Anti-Arrhythmia Agents)
RN  - 98PI200987 (Lidocaine)
RN  - AV0X7V6CSE (pilsicainide)
SB  - IM
MH  - Adult
MH  - Anti-Arrhythmia Agents/administration & dosage/*adverse effects/*pharmacokinetics
MH  - Area Under Curve
MH  - *Asian People
MH  - Chromatography, High Pressure Liquid
MH  - Dose-Response Relationship, Drug
MH  - Electrocardiography
MH  - Humans
MH  - Japan
MH  - Korea
MH  - Lidocaine/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics
MH  - Male
MH  - Reference Values
MH  - Young Adult
EDAT- 2009/04/28 09:00
MHDA- 2009/06/12 09:00
CRDT- 2009/04/28 09:00
PHST- 2008/12/18 00:00 [accepted]
PHST- 2009/04/28 09:00 [entrez]
PHST- 2009/04/28 09:00 [pubmed]
PHST- 2009/06/12 09:00 [medline]
AID - S0149-2918(09)00090-3 [pii]
AID - 10.1016/j.clinthera.2009.03.015 [doi]
PST - ppublish
SO  - Clin Ther. 2009 Mar;31(3):609-18. doi: 10.1016/j.clinthera.2009.03.015.