Possible interethnic differences in quinidine-induced QT prolongation between healthy Caucasian and Korean subjects.
OBJECTIVE
The aim of this study was to evaluate the pharmacokinetics and pharmacodynamics of quinidine-induced QT prolongation in healthy Caucasian and Korean subjects to investigate interethnic differences in susceptibility to drug-induced arrhythmia.


METHODS
A randomized, double-blind crossover study was conducted in 24 (12 male and 12 female) Korean and 13 (seven male and six female) Caucasian subjects. After a 20 min infusion of quinidine (4 mg kg(-1)) or saline, the serum concentration of quinidine and the QT interval corrected by Bazett's formula (QTc) were monitored. The dynamic data were analyzed by means of a population modelling approach using NONMEM.


RESULTS
There were no statistical differences in the pharmacokinetic profiles of quinidine between ethnic groups. The QTc values in Caucasians were higher than those in Koreans at the same quinidine concentrations, especially at higher quinidine concentrations and in female subjects. According to an E(max) model [equation: see text], the population modelling approach revealed that E0 (ms) was related to gender (408 + [34*(1 - Sex)]; 1 for male and 0 for female), DeltaE(max) (ms) was related to ethnicity ((136*f(ETHN)) + C(female): f(ETHN) = 1 for Koreans and 1.26 for Caucasians; C(female) was 106 only for Caucasian females), and EC50 was estimated to be 3.13 microm.


CONCLUSIONS
These results suggest that Korean subjects were less sensitive to quinidine-induced QT prolongation than Caucasian subjects, and that this trend was particularly true for females. Further population-based studies are merited to characterize more completely the ethnic differences in drug-induced QT prolongation between Asians and other ethnic groups.
Shin
Jae-Gook
JG
Department of Pharmacology and Pharmacogenomics Research Centre, Inje University College of Medicine, Busan, Korea.
Kang
Won-Ku
WK
Shon
Ji-Hong
JH
Arefayene
Million
M
Yoon
Young-Ran
YR
Kim
Kyung-Ah
KA
Kim
Doo-Il
DI
Kim
Dong-Soo
DS
Cho
Kwang-Hyun
KH
Woosley
Raymond L
RL
Flockhart
David A
DA
D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D044466:Asian People / Q000208:ethnology; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000208:ethnology; D008297:Male; D011802:Quinidine / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D044465:White People / Q000208:ethnology
D000889:Anti-Arrhythmia Agents; D011802:Quinidine