Pronounced differences between native Chinese and Swedish populations in the polymorphic hydroxylations of debrisoquin and S-mephenytoin.
The frequency of poor metabolizers of debrisoquin was low and similar in four different native Chinese nationalities. In a total sample of 695 Chinese subjects, only seven (1.01%) had a urinary ratio between debrisoquin and 4-hydroxydebrisoquin greater than 12.6, which is the antimode between poor metabolizers and extensive metabolizers in white populations. This is significantly lower than the 6.82% found in 1011 white Swedish healthy subjects (p less than 0.0001). Admixture analysis indicated the occurrence of two distributions within extensive metabolizers among both Chinese and white subjects. The mean of the distribution of metabolic ratios among Chinese extensive metabolizers was shifted toward higher values compared with Swedish extensive metabolizers (p less than 0.01). The frequency of poor metabolizers of S-mephenytoin was higher in 137 Chinese (14.6%) than in 488 Swedish (3.3%) subjects (p less than 0.0001). Our findings imply that drugs metabolized by these two polymorphic hydroxylases should be prescribed in different dosages to Chinese and white subjects.
Department of Clinical Pharmacology, Karolinska Institute, Huddinge Hospital, Sweden.
L
L
Bertilsson
Y Q
YQ
Lou
Y L
YL
Du
Y
Y
Liu
T Y
TY
Kuang
X M
XM
Liao
K Y
KY
Wang
J
J
Reviriego
L
L
Iselius
F
F
Sjöqvist
D002681:China / Q000208:ethnology; D002849:Chromatography, Gas; D003647:Debrisoquin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D006801:Humans; D006900:Hydroxylation; D008617:Mephenytoin / Q000378:metabolism*; D010641:Phenotype; D011110:Polymorphism, Genetic; D013548:Sweden / Q000208:ethnology
C012359:4-hydroxydebrisoquin; D008617:Mephenytoin; D003647:Debrisoquin