TY - JOUR
T1 - Dose-response relationships of propranolol in Chinese subjects with different CYP2D6 genotypes
AU - Huang, Chin Wei
AU - Lai, Ming Liang
AU - Lin, Min Shung
AU - Lee, Hwei Ling
AU - Huang, Jin Ding
PY - 2003/1/1
Y1 - 2003/1/1
N2 - Background. For clinical treatment, a smaller dosage of propranolol is often used among Chinese people. Propranolol is metabolized by polymorphic CYP2D6. We postulate that the lower propranolol dosage in Chinese is due to a slower CYP2D6 metabolism. A majority of the Chinese population has the nucleotide T188 in the CYP2D6 gene (CYP2D6*10) instead of C188 (CYP2D6*1), which most white subjects have. Chinese subjects of different CYP2D6*1/CYP2D6*10 genotypes have been shown to have different propranolol pharmacokinetic characteristics. In this study, we compared the β-blockade effects of propranolol in Chinese subjects of the two different CYP2D6 genotypes. Methods. Based on the nucleotide 188 genotypes, two groups of 10 healthy subjects each were selected. Each subject was given a 10-, 20-, or 40-mg rac-propranolol tablet three times a day for 3 days in 3 different phases. Heart rate and blood pressure were measured in both supine and upright positions. The heart rate was also determined during treadmill exercise test. Plasma concentration of S-propranolol at 2 hrs after the last-dose administration was measured. Results. Despite therebeing higher S-propranolol plasma concentration in CYP2D6*10 subjects than in CYP2D6*1 subjects at 10- and 20-mg dosage, the dose-response relationship was not significantly different in these subjects. Conclusions. Our results do not support the hypothesis that CYP2D6*1/CYP2D6*10 polymorphism may affect the β-blockade effect of propranolol in Chinese subjects.
AB - Background. For clinical treatment, a smaller dosage of propranolol is often used among Chinese people. Propranolol is metabolized by polymorphic CYP2D6. We postulate that the lower propranolol dosage in Chinese is due to a slower CYP2D6 metabolism. A majority of the Chinese population has the nucleotide T188 in the CYP2D6 gene (CYP2D6*10) instead of C188 (CYP2D6*1), which most white subjects have. Chinese subjects of different CYP2D6*1/CYP2D6*10 genotypes have been shown to have different propranolol pharmacokinetic characteristics. In this study, we compared the β-blockade effects of propranolol in Chinese subjects of the two different CYP2D6 genotypes. Methods. Based on the nucleotide 188 genotypes, two groups of 10 healthy subjects each were selected. Each subject was given a 10-, 20-, or 40-mg rac-propranolol tablet three times a day for 3 days in 3 different phases. Heart rate and blood pressure were measured in both supine and upright positions. The heart rate was also determined during treadmill exercise test. Plasma concentration of S-propranolol at 2 hrs after the last-dose administration was measured. Results. Despite therebeing higher S-propranolol plasma concentration in CYP2D6*10 subjects than in CYP2D6*1 subjects at 10- and 20-mg dosage, the dose-response relationship was not significantly different in these subjects. Conclusions. Our results do not support the hypothesis that CYP2D6*1/CYP2D6*10 polymorphism may affect the β-blockade effect of propranolol in Chinese subjects.
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M3 - Article
C2 - 12728976
AN - SCOPUS:0037981622
SN - 1726-4901
VL - 66
SP - 57
EP - 62
JO - Journal of the Chinese Medical Association
JF - Journal of the Chinese Medical Association
IS - 1
ER -