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Background. Quercetin is abundant in plants and human diets. Previous studies indicated that quercetin inhibited the activity of CYP1A2, and the combination of quercetin with the substrates of CYP1A2 might produce herb-drug interactions. This research aims to determine the effects of quercetin and the CYP1A2 gene polymorphisms, namely, CYP1A2*1C (−2964G>A) and 1F* (734C>A), on the metabolism of caffeine. Method. The experiment was designed into two treatment phases separated by a 2-week washout period. Six homozygous individuals for the CYP1A2*1C/1F* (GG/AA) genotype and 6 heterozygous individuals for the CYP1A2*1C/1F* (GA/CA) genotype were enrolled in the study. Quercetin capsules (500 mg) were given to each volunteer once daily for 13 consecutive days, and after that, each subject was coadministrated 100 mg caffeine capsules with 500 mg quercetin on the 14th day. Then a series of venous blood samples were collected for HPLC analysis. Correlation was determined between pharmacokinetics of caffeine and paraxanthine with caffeine metabolite ratio. Results. Quercetin significantly affected the pharmacokinetics of caffeine and its main metabolite paraxanthine, while no differences were found in the pharmacokinetics of caffeine and paraxanthine between GG/AA and GA/CA genotype groups. Conclusion. Quercetin significantly inhibits the caffeine metabolism, which is unrelated to CYP1A2*1C (−2964G>A) and 1F* (734C>A) gene polymorphisms.

Data on both the incidence of slow acetylator phenotype of probe drugs isoniazid, sulfadimidine or sulfamethazine, caffeine and dapsone in mainland or overseas Chinese, and the distribution of NAT2 genotypes and the frequency of NAT2 alleles in the Chinese populations were summarized and reanalysed using a meta-analysis method. Frequency of the slow acetylator phenotype in 3516 healthy Han Chinese gave an overall mean of approximately 19.9 +/- 4.0%, with the range of the combined data being between 15.8% and 25.5%. In addition, frequencies of the slow acetylator phenotype differ between the different minorities in Chinese populations and the range was between 3.2% and 50.6%, with a mean value of 20.6 +/- 12.9% in a total of 1842 individuals from 17 Chinese minorities. In addition, there was no significant heterogeneity in overseas Chinese between the probe drugs isoniazid and sulfadimidine or sulfamethazine (chi 2 = 5.97, df = 4; p0.05), and the mean value of slow acetylator phenotype incidence was 24.5% (119/485; 95% CI: 20.7-28.3%), consistent with that of the native Chinese. As expected, frequency of the slow acetylator genotypes in Chinese populations was 25.4% (112/441; 95% CI: 21.3-29.5%), which was in accordance with that of the slow acetylator phenotype in native or overseas Chinese. For all genotypes, *4/*4 (29.9%, 132/441), *4/*6A (27.4%, 121/441), *4/*7A (12%, 53/441) and *6A/*6A (11.3%, 50/441) occupied 80.6%, but *5A/*7A (0.2%, 1/441), *5A/*5A (1.1%, 5/441) and *7A/*7A (1.8%, 8/441) were not frequently found. From this report, the genotype frequencies of homozygous rapid acetylator, heterozygous rapid acetylator, and homozygous slow acetylator were found to be 0.299 (132/441), 0.447 (197/441) and 0.254 (112/441), respectively. Furthermore, both *4 (52.3%; 95% CI: 49-56%) and *6A (30.5%; 95% CI: 28-34%) were major NAT2 alleles, while *7A (11.2%; 95% CI: 9-13%) and *5A (6%; 95% CI: 4-8%) were uncommonly present. Frequency of the mutant alleles was observed at 0.477 (421/882 alleles). The *7A constituted 23.5% t(99/421) of slow acetylator alleles in Chinese populations, showing that this point mutation exists not only in Oriental or Asiatic, but also in Chinese populations. According to the Hardy-Weinberg equilibrium, in the phenotyped Chinese populations, the mean estimate of predicted allelic frequencies of the genotypes RR, Rr, and rr was 0.294, 0.496, and 0.210 for the Chinese, and the expected frequency of the deficient gene r was 0.458. By comparison, the predicted values are in complete agreement with the observed ones. In conclusion, this meta-analysis determined the accurate population frequencies of phenotype and genotype of the NAT2 genetic deficiency in healthy Chinese subjects.

To improve and validate an analytical method based on liquid chromatography and electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for the quantitative measurement of ilaprazole and its two metablites in human plasma.Separation of analytes and the internal standard (IS), omeprazole, was performed on a Thermo HyPURITY C18 column (150x2.1 mm, 5 microm) with a mobile phase consisting of 10 mmol/L ammonium formate water-acetonitrile solution (50:50, v/v) at a flow rate of 0.25 mL/min. The API4000 triple quadruple mass spectrometer was operated in multiple reactions monitoring mode via positive electrospray ionization interface using the transition m/z 367.2 --m/z184.0 for ilaprazole, m/z 383.3 --m/z 184.1 for ilaprazole sulfone, m/z 351.2 --m/z 168.1 for ilaprazole thiol ether and m/z 346.2 --m/z 198.0 for omeprazole.The method was linear over the concentration range of 0.23-2400.00 ng/mL for ilaprazole, 0.05-105.00 ng/mL for ilaprazole thiol ether and 0.06-45.00 ng/mL for ilaprazole sulfone. The intra- and inter-day precisions were all less than 15% in terms of relative standard deviation (RSD), and the accuracy was within 15% in terms of relative error (RE) for ilaprazole, ilaprazole sulfone and ilaprazole thiol ether. The lower limit of quantification (LLOQ) was identifiable and reproducible at 0.23, 0.05 and 0.06 ng/mL with acceptable precision and accuracy for ilaprazole, ilaprazole sulfone and ilaprazole thiol ether, respectively.The validated method offered sensitivity and a wide linear concentration range. This method was successfully applied for the evaluation of the pharmacokinetics of ilaprazole and its two metabolites after single oral doses of 5 mg ilaprazole to 12 healthy Chinese volunteers.

Genetic polymorphisms causing Ser49Gly and Gly389Arg mutants of beta(1)-adrenoceptor may result in significant changes in the function of this receptor. The aim of the present study was to investigate the frequencies of the Ser49Gly and Gly389Arg mutant alleles in healthy Chinese populations and to investigate the differences between 2 Chinese ethnic groups (Han and Dai populations) with respect to the frequencies of these alleles.A total of 225 Han Chinese and 175 Dai Chinese unrelated healthy volunteers were recruited for this study. Genomic DNA was extracted from peripheral blood leukocytes by using a standard manual chloroform-phenol extraction. Fragments spanning the 2 polymorphisms were amplified by using polymerase chain reaction with template genomic DNA and relevant primers. The DNA products including the polymorphic loci were subjected to restriction endonuclease digestion with Eco0109I and BcgI. Digested fragments were detected with an ultraviolet detector after electrophoresis (100 V for approximately 1.5 h).The frequencies of the Gly49 and Arg389 alleles were, respectively, 16.2% and 76.4% in the Han population and 14.6% and 75.7% in the Dai population.The polymorphisms causing the Ser49Gly and Gly389Arg mutations of the beta(1)-adrenoceptor existed in both healthy Han and Dai Chinese populations. The frequencies of the Ser49Gly and Gly389Arg mutant alleles were not significantly different in the Han and Dai populations. However, the frequency of the Gly389 variant seems to be significantly lower in these 2 populations than in an African-American population.

Either G-2964 or A734 in the human CYP1A2 gene was confirmed to be associated with high inducible enzyme activity in smokers, but not in nonsmokers. In this study, for the first time, we observed an association between phenotypes and genotypes of CYP1A2 with respect to the two genetic polymorphisms in 163 healthy Chinese volunteers living in Qidong. The ratio of plasma 17X/137X at 6 h after oral administration of 300 mg caffeine was employed in CYP1A2 phenotyping analysis, while genotyping analysis was carried out by polymerase chain reaction-restriction fragment length polymorphism. The allele frequencies of A at -2964 and A at 734 in 139 non-smoking subjects were 0.25 and 0.67, respectively. The A/A-2964C/C734, G/A-2964C/C734 or A/A-2964C/A734 genotype that was thought to have lower inducibility/activity of CYP1A2 than the other genotypes did not exist in the tested Chinese subjects. The ratio of 17X/137X was 0.46 +/- 0.26 in G/G-2964A/A734 genotypes (n = 22) and 0.36 +/- 0.19 in non-G/G-2964A/A734 (n = 117). In addition, there was significant difference between them (P = 0.036). A similar result was also achieved in 24 smokers. Since Qidong is a special region with particularly high incidence of hepatocellular carcinoma in China, the association of phenotypes with genotypes of CYP1A2 in the Qidong population might result from some inducible environmental factors such as those of cigarettes in smokers.