Ethnic differences and relationships in the oral pharmacokinetics of nifedipine and erythromycin.
OBJECTIVE
Our objective was to investigate ethnic differences in the oral pharmacokinetics of nifedipine and erythromycin, both typical cytochrome P4503A (CYP3A) substrates, in Koreans and Caucasians and to identify the nature of any correlations between the pharmacokinetic parameters of the two drugs.


METHODS
Twenty healthy male volunteers (10 Koreans and 10 Caucasians) received single oral doses of nifedipine (10 mg) or erythromycin (500 mg) in a randomized 2-way crossover study. Pharmacokinetic evaluations were performed, and parameters were compared for the two ethnic groups. During the nifedipine study period, hemodynamic measurements were conducted to determine the pharmacodynamic relevance of the pharmacokinetic differences.


RESULTS
Koreans showed area under the concentration-time curves (AUCs) for both drugs that were 1.6 to 1.7 times higher than those of Caucasians. This difference decreased to 1.3 when normalized for body weight. Significant correlation between the AUCs of the two drugs was not evident. Hemodynamic changes after nifedipine administration paralleled those of the pharmacokinetic differences, with significantly greater decreases in blood pressure and total peripheral resistance noted in Koreans.


CONCLUSIONS
Koreans showed significantly lower oral clearances of nifedipine and erythromycin, probably because of genetic differences attributed to the CYP3A enzymes.
Yu
K S
KS
Department of Pharmacology, Clinical Pharmacology Unit, and Clinical Trial Center/Clinical Research Institute, Seoul National University College of Medicine and Hospital, Seoul, Korea.
Cho
J Y
JY
Shon
J H
JH
Bae
K S
KS
Yi
S Y
SY
Lim
H S
HS
Jang
I J
IJ
Shin
S G
SG
D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D001835:Body Weight / Q000502:physiology; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004917:Erythromycin / Q000493:pharmacokinetics*; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D009543:Nifedipine / Q000493:pharmacokinetics*; D013608:Tablets, Enteric-Coated; D044465:White People
D000900:Anti-Bacterial Agents; D002121:Calcium Channel Blockers; D013608:Tablets, Enteric-Coated; D004917:Erythromycin; D009543:Nifedipine