广东连南汉族和瑶族儿童硫嘌呤甲基转移酶研究

目的本文对硫嘌呤甲基转移酶(Thiopurine S-methyltransferase,TPMT)在广东连南地区健康汉族儿童(n=87)和瑶族儿童(n=1 26)中的活性分布和4种常见TPMT基因突变的等位基因频率进行研究.方法采用高效液相色谱法测定红细胞的TPMT活性;采用等位基因特异性的PCR(allelespecific PCR,ASPCR)方法和限制性片断长度多态性(PCR-restrictionfragmentlength polymorphism,RFLP)的方法检测TPMT*2(G238C)、TPMT*3A(A719G/G460A)、TPMT*3B(G460A)和TPMT*3C(A719G)的等位基因频率.结果健康汉族儿童和瑶族儿童的TPMT活性都呈正态分布,活性的平均值分别为13.01±2.80U.ml-1pRBC和13.54±3.89U.ml-1 pRBC,两者的差异无显著性.在健康汉族儿童中只找到1例TPMT*3C杂合子(该汉族儿童的TPMT活性为12.36U.ml-1 pRBC),没有找到TPMT*2、TPMT*3A和TPMT*3B,汉族儿童总的TPMT基因突变频率是0.6%.在健康瑶族儿童中没有找到这几种突变.结论广东连南地区汉族和瑶族儿童TPMT的活性分布和总的TPMT基因突变频率没有显著性差异.     

Frequencies of thiopurine S-methyltransferase mutant alleles (TPMT*2, *3A, *3B and *3C) in 151 healthy Japanese subjects and the inheritance of TPMT*3C in the family of a propositus

AIMS: To determine the frequencies of four thiopurine S-methyltransferase (TPMT) mutant alleles, TPMT*2, *3A, *3B and *3C in a normal Japanese population. METHODS: Genotypes were determined in 151 Japanese subjects and in six family members of a propositus using polymerase chain reaction (PCR)-restriction fragment length polymorphism and allele-specific PCR assays. RESULTS: Only one TPMT*3C heterozygote was identified (gene frequency 0.3%). TPMT*2, *3A and *3B were not detected. In addition, TPMT*3C was found to have been inherited from the mother and passed on to the son of the propositus. CONCLUSIONS: TPMT*3C appears to be most prevalent among the known mutant allele of TPMT in a Japanese population which may have some relevance for the treatment of Japanese patients with thiopurine drugs.     

中国新疆维吾尔族硫嘌呤甲基转移酶基因突变研究

目的 研究硫嘌呤甲基转移酶(thiopurine S-methyltransferase，TPMT)在新疆维吾尔族中的基因突变频率。方法 用等位基因特异性的PCR方法和限制性片断长度多态性的方法检测4种常见的导致酶活性降低的突变类型：TPMT*2、TPMT*3A、TPMT*3B和TPMT*3C。结果 在160名维吾尔族中发现了1例TPMT*3A(A719G／G460A)杂合子、5例TPMT*3C(A719G)杂合子，TPMT*3A和TPMT*3C的等位基因频率分别是0．3％和1．6％。结论 维吾尔族总的TPMT突变等位基因频率(1．9％)同中国其他民族相近；TPMT*3C是维吾尔族最主要的突变类型。     

中国健康汉族和瑶族人群巯基嘌呤甲基转移酶活性的分布

目的研究巯基嘌呤甲基转移酶(TPMT)活性在中国汉族和瑶族人群中的分布。方法建立改良的反相高效液相色谱法,测定人红细胞(RBC)中TPMT活性。结果测定了273名中国健康汉族成年人、88名汉族儿童和148名健康瑶族儿童红细胞中TPMT活性,未发现酶缺陷者,其平均活性分别为(11.96±3.27),(13.02±2.78)和(13.27±3.92)nmol·(h·mL)-1packed红细胞。瑶族儿童TPMT活性较同龄汉族儿童差异无显著性;TPMT活性在中国汉族和瑶族人群中都呈正态分布;在中国汉族和瑶族人群中均未发现有与性别有关的差异;汉族人群TPMT活性与年龄无关;瑶族儿童TPMT活性与年龄呈正相关,但相关关系较弱。结论中国汉族和瑶族人TPMT活性分布均呈正态分布。     

Thiopurine S-methyltransferase pharmacogenetics: Functional characterization of a novel rapidly degraded variant allozyme

A novel human thiopurine S-methyltransferase (TPMT) variant allele, (319 T > G, 107Tyr > Asp, *27), was identified in a Thai renal transplantation recipient with reduced erythrocyte TPMT activity. The TPMT*27 variant allozyme showed a striking decrease in both immunoreactive protein level and enzyme activity after transient expression in a mammalian cell line. We set out to explore the mechanism(s) responsible for decreased expression of this novel variant of an important drug-metabolizing enzyme. We observed accelerated degradation of TPMT*27 protein in a rabbit reticulocyte lysate. TPMT*27 degradation was slowed by proteasome inhibition and involved chaperone proteins—similar to observations with regard to the degradation of the common TPMT*3A variant allozyme. TPMT*27 aggresome formation was also observed in transfected mammalian cells after proteasome inhibition. Inhibition of autophagy also decreased TPMT*27 degradation. Finally, structural analysis and molecular dynamics simulation indicated that TPMT*27 was less stable than was the wild type TPMT allozyme. In summary, TPMT*27 serves to illustrate the potential importance of protein degradation - both proteasome and autophagy-mediated degradation - for the pharmacogenetic effects of nonsynonymous SNPs.     

Methylation of 6-mercaptopurine and 6-thioguanine by thiopurine S-methyltransferase A comparison of activity in red blood cell samples of 199 blood donors

Objectives: To compare 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) as substrates for the methylation reaction catalysed by the enzyme thiopurine S-methyltransferase (TPMT). Methods: TPMT activity in haemolysed red blood cells of healthy blood donors was determined twice, using the same experimental setting and equal molar concentrations of 6-TG and 6-MP as substrates. After extraction, the reaction products 6-methyl-TG and 6-methyl-MP were quantified using specific high-performance liquid chromatography procedures. Results: The medians of the TPMT activities from 199 blood donors were 54.4 nmol 6-MTG g⁻¹Hb h⁻¹ when measured with 6-TG as the substrate and 35.8 nmol 6-MMP g⁻¹ Hb h⁻¹ when measured with 6-MP. The correlation coefficient for the 199 pairs of values was 0.8695. On average, TPMT activity was 34% lower with 6-MP as substrate than with 6-TG as substrate. Received: 4 October 1999 / Accepted in revised form: 15 March 2000     

Genotypic and phenotypic analysis of the polymorphic thiopurine S-methyltransferase gene (TPMT) in a European population

1. Characterization of allelic variants of the TPMT gene (TPMT) responsible for changes in TPMT activity, and elucidation of the mechanism by which these alleles act, are required because of the clinical importance of this polymorphism for patients receiving thiopurine drugs.
2. We defined the mutational and allelic spectrum of TPMT in a group of 191 Europeans. Using PCR–SSCP, we screened for mutation the entire coding sequence, the exon-intron boundaries, the promoter region and the 3′-flanking region of the gene. Six mutations were detected throughout the ten exons and seven TPMT alleles were characterized. Four of them, TPMT*2, *3A, *3C and *7, harbouring the known mutations, G238C, G460A, A719G or T681G, were nonfunctional and accounted for 0.5, 5.7, 0.8 and 0.3% of the allele totality, respectively.
3. Within the promoter region, six alleles corresponding to a variable number of tandem repeats (VNTR), were identified. VNTR*V4 and *V5a which harbour four or five repeats of a 17–18 bp unit, were the most frequent (55% and 34%, respectively). The other VNTR alleles, having from five to eight repeats, were rarer.
4. The TPMT phenotype was correctly predicted by genotyping for 87% of individuals. A clear negative correlation between the total number of repeats from both alleles and the TPMT activity level was observed, indicating that VNTRs contribute to interindividual variations of TPMT activity. Therefore, additional analysis of the promoter region of TPMT can improve the phenotype prediction rate by genotyping.

     

MDR1 genotypes do not influence the absorption of a single oral dose of 600 mg valacyclovir in healthy Chinese Han ethnic males

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The absorption of valacyclovir presents a highly negative correlation with the level of P-glycoprotein expression.
• It has been confirmed that a polymorphism of the MDR1 gene in exon 26 is related to the level of P-glycoprotein expression in intestine.
• This study was conducted to find the relationship between polymorphism of MDR1 gene and absorption of valacyclovir.

WHAT THIS STUDY ADDS

• Linkage disequilibrium exists between G2677T/A in exon 21 and C3435T in exon 26, between C1236T in exon 12 and C3435T, but not between C1236T and G2677T/A of MDR1 gene in the Chinese Han ethnic population.
• Three single nucleotide polymorphisms of MDR1 gene do not influence the absorption of valacyclovir in the healthy Chinese Han ethnic population.

AIMS

To investigate the influence of three single nucleotide polymorphisms (SNPs) in exon 12 (C1236T), exon 21 (G2677T/A) and exon 26 (C3435T) of MDR1 gene on the absorption of valacyclovir after a single oral administration in the Chinese Han ethnic population.

METHODS

Two hundred healthy Chinese subjects were genotyped for the SNPs of C1236T, G2677T/A and C3435T in the MDR1 gene using allele-specific polymerase chain reaction. Linkage disequilibrium (LD) was analysed. Twenty-four subjects derived from a large random sample (n = 200) received a single oral dose of 600 mg valacyclovir. Plasma concentrations of acyclovir were determined up to 14 h after administration to obtain a pharmacokinetic profile.

RESULTS

LD existed between G2677T/A in exon 21 and C3435T in exon 26 (P < 0.001), between C1236T in exon 12 and C3435T (P < 0.001), but not between C1236T and G2677T/A (P > 0.05). C_max, AUC_{0–1.5 h} and AUC_0–∞ were used as indices of valacyclovir absorption. AUC_0–∞ for the 2677TA genotype was 17.45 ± 2.40 µg × h/ml, which was much higher compared with the 2677GG, GA and TT genotypes of 10.44 ± 1.00, 11.84 ± 2.83, 11.34 ± 2.32 µg × h/ml, respectively (P < 0.05). Similarly, a statistically significant difference of AUC_0–∞ was also observed for different linked genotypes at position 2677 vs. 3435, and 1236 vs. 3435 (P < 0.05). However, there was no significant difference in valacyclovir absorptive pharmacokinetics between carriers and noncarriers of different haplotypes (P > 0.05).

CONCLUSIONS

Three SNPs of MDR1 gene did not influence the absorption of a single oral dose of 600 mg valacyclovir in healthy Chinese Han ethnic subjects.     

NUDT15 c.415C>T和TPMT*3C基因多态性与汉族人群服用硫唑嘌呤致白细胞减少关联性研究

目的：探讨NUDT15 c.415C>T和TPMT*3C基因多态性与汉族人群服用硫唑嘌呤致白细胞减少的关联性。方法：选取2017年5月-2018年5月在福建医科大学附属第一医院就诊,接受硫唑嘌呤治疗2周以上的汉族患者,PCR-RFLP法检测患者NUDT15 c.415C>T和TPMT*3C基因型,HPLC法测定患者红细胞内6-硫鸟嘌呤核苷酸谷浓度。根据白细胞值分组,结合临床资料,分析2种基因多态性与硫唑嘌呤致白细胞减少的相关性。结果：共纳入患者129例,白细胞减少组15例（11.6%）,白细胞正常组114例（88.4%）,2组在性别、年龄、日剂量、是否联合使用美沙拉秦或柳氮磺吡啶、沙利度胺、英夫利西及TPMT*3C基因多态性等均无显著性差异（P>0.05）。白细胞减少组53.3%（8/15）携带NUDT15 c.415>T突变基因,与白细胞正常组14.9%（17/114）差异有显著性（P=0.000 372）。携带该等位基因突变型患者出现白细胞减少风险高于携带野生型患者（OR=6.2,95%CI：2.5~15.4,P=0.000 054）,更易发生Ⅲ度以上严重的白细胞减少（P=0.000 022）。同一剂量范围野生型患者与突变型患者的6-硫鸟嘌呤核苷酸谷浓度并没有显著性差异（P>0.05）。NUDT15 c.415>T预测白细胞减少特异度为85.1%,敏感度为53.3%,ROC曲线AUC为0.69。结论：NUDT15c.415C>T基因多态性检测对降低汉族人群服用硫唑嘌呤致白细胞减少的风险具有较好的临床价值。     

中国汉族儿童CYP3A5*3基因型与急性淋巴细胞白血病易感性的关联研究

目的:在中国汉族儿童中探讨白血病易感性与CYP3A5*3的频率之间的相关性.方法:共收集172名中国汉族儿童血液,包括52名急性白血病患者(27女性,25男性)和120名健康儿童(53女性,67男性).提取DNA,然后用PCR-RFLP方法检测基因型.结果:CYP3A5*3在人群中的分布符合Hardy-Weinberg平衡.儿童白血病中CYP3A5*3频率为0.721 (95％ CI:0.549,0.893),而健康儿童中为0.758 (95％CI:0.674,0.842),两者之间无明显差异,并且也无男女性别差异.结论:CYP3A5*3是健康儿童和白血病患者中的常见基因型,健康儿童和白血病患儿中CYP3A5*3频率一致, 因此CYP3A5*3与儿童白血病易感性之间无关联.     

Single nucleotide polymorphisms of the pregnane x receptor gene in Han Chinese and a comparison with other ethnic populations

The pregnane X receptor (PXR/NR1I2) gene is a master regulator for a number of cytochrome P450s (CYPs) and drug transporters. This study aimed to detect the single nucleotide polymorphisms (SNPs) of the PXR gene in Han Chinese (n = 186) and to compare the frequencies of polymorphisms of the PXR gene with those in Caucasian and African Americans reported in the literature. The SNPs of the PXR gene were analyzed using the polymerase chain reaction (PCR) and direct sequencing analysis. The mutant frequencies of A11156C and T11193C in Han Chinese were 55% (95% confidence interval (CI): 0.49-0.61) and 59% (95% CI: 0.52-0.64), respectively, higher than those of Caucasian Americans (16 and 16%, respectively) and African Americans (33 and 30%, respectively). However, the reported SNPs in exons 2 and 4 (PXR*2,*3,*4,*6,*9,*10,and *11) were not detected in Han Chinese. These results indicate that there are marked differences in the mutant frequencies of A11156C and T11193C of PXR between Han Chinese and other ethnic groups. The mutant frequency in the coding region (exons 2 and 4) of PXR was very low in Han Chinese. Further studies are needed to determine the impact of common SNPs of PXR in Han Chinese and other ethnic populations on the phenotypic activity of cytochrome P450s and drug transporters transactivated by PXR.     

中国华东汉族人群细胞色素酶CYP3A4新基因型的发现与序列分析

目的:探讨中国华东地区汉族人群细胞色素P4503A4基因的基因型差异。方法:采用RT-PCR与DNA测序技术相结合的方法对来自华东地区的6份汉族成人肝组织P4503A4基因的cD-NA进行了扩增与序列分析。结果:本研究从6份汉族人肝组织中首次检测到了一种新的基因型,该基因型存在三处氨基酸突变和一处核苷酸缺失,即第71位氨基酸发生V(GTG)→A(GCG)突变;第225位氨基酸发生V(GTC)→I(AIC)的突变;第393位氨基酸发生W(TGG)→V(GTG)突变;第671～673位核苷酸CAG发生缺失。结论:本研究首次发现中国华东地区汉族人群存在一种CYP3A4新基因型。     

Distribution of CYP2C9*13 allele in the Chinese Han and the long-range haplotype containing CYP2C9*13 and CYP2C19*2

Cytochrome P450 2C9 (CYP2C9) and CYP2C19, located in tandem on chromosome 10q23–24, are known as genetically polymorphic. CYP2C9*13 is an important CYP2C9 variant in Asian populations, and is correlated with the reduced plasma clearance of some clinically important drugs. In this research, the allele frequency of CYP2C9*13 was determined to be 0.42% (95% CI of 0.17% to 0.86%) in 839 Chinese Han, male subjects. All detected subjects with CYP2C9*13 carry the CYP2C19*2 allele, too. Sequencing results infer the CYP2C9*13 haplotype, which contains eight linked SNPs, originates from the CYP2C9*1B haplotype group. CYP2C9*1B has been reported to be linked with CYP2C19*2. These indicate a long‐range haplotype containing the CYP2C9*13 and CYP2C19*2 mutation, which means most CYP2C9*13 carriers will carry the CYP2C19*2 allele and the six SNPs of the CYP2C9*1B haplotype group, and may have more reduced intrinsic clearance of drugs such as phenytoin, tolbutamide and chlorpropamide that are metabolized by both CYP2C9 and CYP2C19. Copyright © 2012 John Wiley & Sons, Ltd.     

氟西汀及其活性代谢产物在汉族健康人体的药动学

目的:探讨氟西汀及其活性代谢产物去甲氟西汀在汉族健康人体的药动学。方法:24名健康男性志愿者单剂量口服盐酸氟西汀分散片20 mg后,采用液相色谱-串联质谱法测定血浆中氟西汀和去甲氟西汀浓度,应用DAS2.0软件计算药动学参数。结果:氟西汀和去甲氟西汀在人体内药-时曲线呈一室模型。除1例慢代谢型受试者外,23名受试者主要药动学参数如下:t1/2分别为(30.8±7.6)和(130.9±42.0)h;tmax分别为(5.5±2.1)和(58.5±31.7)h;Cmax分别为(11.8±3.5)和(14.2±5.0)ng.mL-1;AUC0-t分别为(487.4±190.2)和(3370.9±1175.8)ng.h.mL-1;AUC0-∞分别为(506.5±208.8)和(3537.8±1424.1)ng.h.mL-1。结论:盐酸氟西汀分散片在人体吸收迅速,消除较慢,而其活性代谢产物去甲氟西汀消除更慢;其中1例受试者呈明显慢代谢型。     

中国健康汉族和维吾尔族人谷胱甘肽硫转移酶的基因多态性

目的 比较中国健康汉族人和维吾尔族人GSTM1、GSTT1和GSTP1基因多态性分布。方法 用多重PCR分析GSTM1和GSTT1基因多态性，PCR—RFLP检测GSTP15号外显子105位密码子基因多态性。结果 汉族人与维吾尔族人的GSTM1纯合缺失频率接近。分别为56.1％和53.2％。而汉族人的GSTT1纯合缺失频率（50．0％）较维吾尔族人（26．6％）高。汉族人GSTP1 105I／I、I／V和V／V基因型频率分别为60．7％，35．2％和4．1％；维吾尔族人分别为51．3％，40．2％and 8．4％。结论 维吾尔族人与汉族人，除GSTM1外，GSTT1与GSTP1突变基因型频率存在明显种族差异。     

咪达唑仑片在中国维吾尔族和汉族健康人体的药动学比较

目的研究健康维吾尔族和汉族志愿者单剂量口服咪达唑仑片的药动学。方法维吾尔族、汉族健康志愿者各10名,男、女各半,单剂量口服15 mg咪达唑仑片后,用HPLC法测定咪达唑仑的血浆浓度,运用DAS 2.0程序以非室模型拟合药动学参数,并对药动学参数进行独立样本t检验和非参数Mann-Whitney U test检验,以判断药动学是否存在显著性的民族差异。结果单剂量口服15 mg咪达唑仑片后,维吾尔族志愿者的主要药动学参数分别为:ρmax(124.8±50.0)μg.L-1,tmax(0.8±0.5)h,t1/2z(1.9±0.7)h,MRT0-12 h(2.8±0.8)h,CL/F(0.9±0.4)L.h-1.kg-1,Vz/F(2.3±0.7)L.kg-1和AUC0-12 h(343.2±150.9)μg.h.L-1。汉族健康受试者的主要药动学参数分别为:ρmax(103.1±26.4)μg.L-1,tmax(1.5±0.7)h,t1/2z(3.0±0.8)h,MRT0-12 h(3.6±0.4)h,CL/F(0.7±0.2)L.h-.1kg-1,Vz/F(2.7±0.8)L.kg-1和AUC0-12 h(368.8±103.4)μg.h.L-1。经检验,维吾尔族的tmax、t1/2z和MRT0-12 h比汉族的短,差异有显著性统计学意义,其余参数的民族差异无显著性统计学意义。两个民族的部分受试者的药-时曲线有双峰。结论单剂量口服咪达唑仑片后,汉族和维吾尔族健康志愿者的药动学存在较大的个体差异,且消除速率的民族差异有显著性统计学意义,临床应用时应注意个体化给药。     

Effects of CYP3A4*1G and CYP3A5*3 polymorphisms on pharmacokinetics of tylerdipine hydrochloride in healthy Chinese subjects

1. The aim of this analysis was to explore the influence of CYP3A4*1G and CYP3A5*3 polymorphisms on the pharmacokinetics of tylerdipine in healthy Chinese subjects.

2. A total of 64 and 63 healthy Chinese subjects were included and identified as the genotypes of CYP3A4*1G and CYP3A5*3, respectively. Plasma samples were collected for up to 120?h post-dose to characterize the pharmacokinetic profile following single oral dose of the drug (5, 15, 20, 25 and 30?mg). Plasma levels were measured by a high-performance liquid chromatography-mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated using non-compartmental method. The maximum concentration (C_max) and the area under the curve (AUC_0–24?h) were all corrected by the dose given.

3. In the wild-type group, the mean dose-corrected AUC_0–24?h was 1.35-fold larger than in CYP3A4*1G carriers (p?=?.018). Among the three CYP3A5 genotypes, there showed significantly difference (p?=?.008) in the t_1/2, but no significant difference was observed for the AUC_0–24?h and C_max. In subjects with the CYP3A5*3/*3 genotype, the mean t_1/2 was 1.35-fold higher than in CYP3A5*1/*1 group (p?=?.007). And the t_1/2 in CYP3A5*3 carriers also was 1.32-fold higher than in the wild-type group (p?=?.004).

4. CYP3A4*1G and CYP3A5*3 polymorphisms may influence tylerdipine pharmacokinetic in healthy Chinese subjects.

     

Non‐antiplatelet effect of clopidogrel: improving endothelial function in Chinese healthy subjects with different CYP2C19 genotype

Clopidogrel has been shown to improve endothelial function in vitro and in patients with coronary artery disease. However, it remains unclear whether such an effect of clopidogrel is associated with CYP2C19 polymorphisms that determine the antiplatelet effect of clopidogrel. After genotyping, 12 healthy participants were enrolled in the study. Among them, six participants were CYP2C19*1/*1 (extensive metabolizers; EM) and the other six participants were CYP2C19*2/*2 or *3 (poor metabolizers; PM). All participants received 300 mg clopidogel orally. Endothelial function was assessed by measurement of flow‐mediated dilation of the brachial artery, and adenosine diphosphate‐induced platelet aggregation was determined by using optical aggregometry at 0, 4 and 24 h after administration of 300 mg clopidogrel. Flow‐mediated dilation was significantly higher at 4 and 24 h after a loading‐dose administration of clopidogrel in both the CYP2C19 EM and PM groups, but showed no significant difference between the two groups. Adenosine diphosphate‐induced platelet aggregation was significantly inhibited at 4 and 24 h after administration of clopidogrel in the CYP2C19 EM group. However, there was no statistical correlation between the change in flow‐mediated dilation and adenosine diphosphate‐induced platelet aggregation in the two CYP2C19 groups. This is the first study to report that clopidogrel improves endothelial function in healthy Chinese subjects, which is unrelated with the CYP2C19 genotype and independent of antiplatelet action.     

单剂量口服奥美拉唑在中国维吾尔族和汉族健康人体内药物动力学考察

目的研究维吾尔族和汉族健康受试者单剂量口服奥美拉唑肠溶片的药物动力学,旨在为战时救治和平时临床合理应用奥美拉唑提供依据。方法健康维吾尔族和汉族受试者各10名,男、女各半,单剂量口服奥美拉唑肠溶片40 mg后,于不同时间点采集静脉血,血浆样品经处理后用HPLC法测定奥美拉唑的质量浓度。用DAS 2.0药物动力学软件处理数据,用SPSS11.5软件统计分析。结果奥美拉唑在维吾尔族受试者体内的主要药物动力学参数分别为:ρmax(728.4±214.3)μg.L-1,tmax(2.8±0.5)h,t1/2(1.2±0.5)h,AUC0-12(1 837.0±861.8)μg.h.L-1,AUC0-∞(1 847.6±869.1)μg.h.L-1;在汉族受试者体内的主要药物动力学参数分别为:ρmax(760.5±581.2)μg.L-1,tmax(2.7±0.8)h,t1/2(1.6±1.3)h,AUC0-12(1 437.6±798.1)μg.h.L-1,AUC0-∞(1 470.1±769.5)μg.h.L-1。结论奥美拉唑在维吾尔族、汉族受试者体内的ρmax、AUC(0-12)、AUC(0-∞)个体间差异较大,但统计学分析结果显示两民族人体内主要药物动力学参数差异无统计学意义。