Dose-response relationships of propranolol in Chinese subjects with different CYP2D6 genotypes.
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 beta-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 beta-blockade effect of propranolol in Chinese subjects.
Department of Neurology, National Cheng-Kung University, Tainan, Taiwan, ROC.
Chin-Wei
CW
Huang
Ming-Liang
ML
Lai
Min-Shung
MS
Lin
Hwei-Ling
HL
Lee
Jin-Ding
JD
Huang
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics; D011110:Polymorphism, Genetic; D011433:Propranolol / Q000493:pharmacokinetics / Q000494:pharmacology*
D011433:Propranolol; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6