Aims: To investigate the incidence of the CYP2C19 polymorphism in the Chinese Dai population. Methods: One hundred and ninety-three healthy Chinese Dai volunteers were identified with respect to CYP2C19 by genotype and phenotype analyses. A polymerase chain reaction-restriction fragment length polymorphism method was performed for genotyping procedures. The 4-hydroxymephenytoin (4-OH-MP) and S/R-mephenytoin (S/R-MP) excreted in the urine were determined by high-performance liquid chromatographyand gas chromatography, respectively. Results: Eighteen subjects were identified as poor metabolisers (PMs). The frequency of PMs in the Chinese Dai subjects was 9.3% (95% confidence interval 5.2, 13.4), which is lowerthan that in the Chinese Han population (P<0.05). Chinese Dai subjects had a higher frequency of the mutant CYP2C19*2 allele (0.303) and a lowerfr equency of the mutant CYP2C19*3 allele (0.034). These two mutant alleles could explain all defi-ciencies of CYP2C19 activity in the Chinese Dai subjects. The frequency of the CYP2C193 allele is significantly lowerthan that in the Chinese Han population (P<0.05). The mean S/R ratio was lower in the homozygous extensive metabolisers (EMs) compared with that in heterozygous EMs (P<0.01), and the latter was lowerthan that in the PMs (P<0.01). Furthermore, the mean S/R ratio in CYP2C193/CYP2C192 heterozygous PMs was possibly lower than that in the CYP2C192/CYP2C19*2 homozygous PMs (P<0.05). Conclusion: The frequencies of PMs and CYP2C19*3 allele in the Chinese Dai population are significantly lowerthan those in the Han population. The CYP2C19genotype analysis is largely consistent with the mephenytoin phenotype analysis. The variability of S/R ratios in EMs and PMs shows a gene-dosage e ect.

The study was designed to define the contribution of cytochrome P450 2C19 (CYP2C19) and cytochrome P450 3A4 (CYP3A4) to citalopram N-demethylation and to evaluate the relationship between the disposition of citalopram and CYP2C19 genotype. A single oral 40mg dose of citalopram was administered to eight extensive metabolizers and five poor metabolizers recruited from 77 healthy Chinese volunteers whose genotypes and phenotypes were predetermined. The plasma concentrations of citalopram and desmethylcitalopram were N determined by high-performance liquid chromatography. It was found that the genotype of CYP2C19 had a significant effect on the N-demethylation of citalopram. Poor metabolizers with m1 mutation had higher area under the plasma concentration versus time curve (AUC03) values than did extensive metabolizers. Terminal eliminationelimination half-life (t1/2) values of citalopram in poor metabolizers were significantly higher than the values in extensive metabolizers who were either homozygous or heterozygous with CYP2C19*1. The oral clearance (CLoral) of citalopram in poor metabolizers was significantly lower than that of extensive metabolizers. The AUC03 and maximum plasma concentration (Cmax) of desmethylcitalopram in poor metabolizers were significantly lower than the values of extensive metabolizers. The results show that CYP3A4 is not the major enzyme in the N-demethylation of citalopram among extensive metabolizers. The polymorphism of CYP2C19 plays an important role in the Ndemethylation of citalopram in vivo. The extensive metabolizers and poor metabolizers of CYP2C19 had significant difference in disposition of citalopram in vivo.

Objectives: Our objectives were to determine whether the Gly389 polymorphism of the β1-adrenergic receptor exhibits reduced responsiveness in vivo and to test the hypothesis that the Gly389Arg polymorphism affects the blood pressure and heart rate response to metoprolol. Methods: β1-Adrenergic receptor genotype was determined by polymerase chain reaction-restriction fragment length polymorphism assay. Exercise-induced heart rate increases were compared to determine the functional significance in vivo in 8 healthy Chinese men homozygous for Gly389 and 8 homozygous for Arg389. All of the subjects were given 25, 50, or 75mg of metoprolol every 8 hours; the dosages were given in a random order, and each dosage was given for β1 day. The degree of β-blockade was measured as the reduction in resting and exercise heart rates and blood pressures. Plasma metoprolol concentrations were measured by the use of HPLC-fluorescence detection. Results: Exercise led to a workload-dependent increase in heart rate. There were no differences in exerciseinduced heart rate increases between Arg389 and Gly389 homozygotes. Oral metoprolol caused significant dose-dependent decreases in both resting and exercise heart rates in both groups. The reductions in the resting heart rate in 3 dosage levels of metoprolol were 6.3%±0.8% versus 4.1% 0.7%, 10.1%±1.0% versus 6.2%±1.1%, and 14.4%±1.4% versus 10.9%±1.3% in homozygous Arg389 subjects and Gly389 subjects, respectively (P=.008). We also found differences with respect to the exercise heart rate (8.9%±0.5%, 14.0%±0.9%, and 20.1%±1.5% in Arg389 subjects and 6.6%±0.7%, 11.7%±1.0%, and 16.4%±1.3% in Gly389 subjects; P=.017) and systolic pressure (5.9%±0.7%, 9.2%±1.0%, and 11.6% 1.2% in Arg389 subjects and 4.6%±0.5%, 6.0%±0.8%, and 9.9%±0.9% in Gly389 subjects; P=.011). However, the difference in the fall in diastolic pressure was not statistically significant (P=.442).

目的：建立同时测定体外肝微粒体中氟西汀及其代谓十产物去甲氟西汀的反相高效液相色谱紫外检测法。方法：含微粒体蛋白和NADPH发生系统及氟西汀的孵育液加入冰乙腈酸终止反应后，再加入去甲替林作为内标并以，z.正己烷和乙腈的混合液进行萃取，然后以反相ODS柱分离，在226nlTl处以紫外检测器进行检测。结果：孵育体系中没有明显的干扰峰出现，氟西汀和去甲氟西汀洗脱快，分离好，线性范围均为10-800ug/L，最低检测限均为5ug/L，相对回收率为94%-104%，变异系数少于9.1%。结论：本法快速，灵敏，回收率高，且萃取过程简单，可用于体外氟西汀的代谢研究。