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Ethnic differences and relationships in the oral pharmacokinetics of nifedipine and erythromycin
Author(s) -
Yu KyungSang,
Cho JooYoun,
Shon JiHong,
Bae KyunSeop,
Yi SoYoung,
Lim HyeongSeok,
Jang InJin,
Shin SangGoo
Publication year - 2001
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1067/mcp.2001.117703
Subject(s) - nifedipine , pharmacokinetics , erythromycin , medicine , pharmacology , crossover study , cyp3a , hemodynamics , oral administration , cytochrome p450 , antibiotics , biology , placebo , metabolism , alternative medicine , pathology , microbiology and biotechnology , calcium
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. Clinical Pharmacology & Therapeutics (2001) 70 , 228–236; doi: 10.1067/mcp.2001.117703