Genetic polymorphisms in drug-metabolizing enzymes,transporters,receptors,and other drug targets have been linked to interindividual differences in the efficacy and toxicity of many medications.Pharmacogenomics is to study of how genes affect the individual response to drugs.There are some evidences that in the future the use of pharmacogenomics could help to enhance the effects of drugs and reduce the adverse drug reactions(ADRs),as it aims to predict which patients are likely to respond to a particular drug and which patients are likely to have significant ADRs.Pharmacogenomics studies are rapidly elucidating the inherited nature of these differences in drug disposition and effects,thereby providing a strong scientific basis for optimizing drug therapy on the basis of each patient's genetic constitution.In this article some examples of genetic polymorphisms which affecting drug pharmacokinetics(in protein binding of drugs in plasma)and pharmacodynamics(correlated with antihypertensive drugs)are briefly illustrated.

Aim To establish a simple reverse dot blot m ethod (RDB) for detecting the genotype of NAT2 in Chinese people. Methods PCR was performed to obtain a biotin labeled DNA fragment. Allele specific oligonucleotide probes were spotted onto a nylon membrane. The DNA fragment hybridized with the membrane under stringent conditions. Finally, a nonradioactive colorimetric reaction was used to detect five mutants of NAT2. NAT2 genotypes of 48 patients with pulmonary tuberculosis were detected with RDB.Results The results obtained from RDB were in consistent with those from allele specific amplification. The NAT2 allele frequencies of *5, *6, *7 were 1.04%, 22.9% and 15.6%, respectively.Homozygous wildtype,heterozygous mutant and homozygous mutant subjects were 33.3%, 54.2% and 12.5%, respectively.Conclusion RDB method was proved to be accurate and convenient, it can be u sed in rational drug therapy.

Gene chip is an important biological technology, which is developing quickly recently. In this article, we reviewed the origin, development, basic operation of gene chip. Several kinds of gene chips including tiled array, direct allele specific fluorescence targeting (DAFT) array, labeled auxiliary oligonucleotides array, ligase detection reaction array, and peptide nucleic acid array were introduced as examples for their use in mutation detection. The prospect of the use of gene chip in optimizing drug therapy was also discussed.

Objective: To evaluate the anti-hepatitis effect of Yinzhiku Compound and obtain pharmacodynamic evidence for its clinical application.Methods: Using the model of HepG2.2.15 cells,we determined the inhibitory effects of the drug extract with water and that with alcohol on HbsAg and HbeAg from the HepG2.2.15 cells by serum pharmacological methods.Results: The inhibition of the two Abstracts on HbsAg reached the peak on the sixth day and gradually dropped afterwards,but still at a high level on the twelfth day.Their inhibitory effect on HbeAg,too,attained the highest level on the sixth day,but did not fall obviously afterwards and remained high even on the twelfth day.Conclusion: Yinzhiku Compound has a high inhibitory effect on both HbsAg and HbeAg,with no evident difference between the drug extract with water and that with alcohol.

NAT2 is an important drug metabolizing enzymes in humans.Polymorphisms in NAT2 gene produce variants at amino acid including seven mutation sites.In vivo NAT2 takes part in 20 kinds of drugs metabolism and activation of carcinogen.Polymorphism of NAT2 has been related to some diseases.This paper reviews the polymorphisms and genotyping about NAT2 and their implications in drug and clinical research.

N-acetyltransferase 2 is an important metabolic enzyme in the human body,participating mainly in the metabolism of medicine containing nitrogen.Presently a lot of researches have been undertaken in the respects like the determination of NAT2 genotype and drug metabolism and so on.In the recent years,more and more attention is paid to the simulation of three-dimension(solid)structure of protein,but the study is just at the outset on three-dimension structure of the NAT2 as well as its structure-function relationship when combined with drug.The research progress of construction of the three-dimension structure of NAT2 is summarized,emphasizing on its methods and tools.

AIM:To study the pharmacokinetics and relative bioavailability of citalopra hydrobromide in human plasma.METHODS:The citalopra hydrobromide concentrations in plasma were determined by HPLC-UV.The column was Lichrospher ODS(5 ?m,250 mm?4.6 mm).The mobile phase was acetonitrile-0.1 mol/L KH2PO4 buffer-triethylamine(35:65:0.3,v/v/v).The flow rate was 1 mL/min.The detection wavelength was 240 nm.The test and reference formulations of citalopra were given to 18 healthy male volunteers.RESULTS:The calibration curve was linear within the range of 2-128 ?g/L,r=0.9992.The minimum detection limit was 1 ?g/L.The recovery was 80%-88%,the RSDs of inter-day and intra-day were not more than 15%.After a single oral dose of 20 mg citalopra hydrobromide was given,the main pharmacokinetic parameters tmax were(4.6?1.0),(4.4?1.4) and(4.0?1.4) h;Cmax were(70?19),(71?17) and(66?21) ?g/L;and t1/2 were(37?9),(37?6) and(36?6) h respectively.CONCLUSION:No significant difference exists among the pharmacokinetic parameters of the three formulations.They are bioequivalent.

AIM: To study the pharmacokinetics and rela ti ve bioavailability of naftopidil in healthy male volunteers. METHODS: The naftopidil concentrations in plasma were determined by HPLC. The test and reference formulations of naftopidil were given to 18 healthy male volunteer s. The calibration curve was linear within the range of 1.6 - 400 ?g?L -1 , r=1. The minimum detection limit was 1 ?g?L -1 . The mean recovery rate was 85.2 %- 89.9 %, RSDs of inter-day and i ntra-day were no more than 8.0 %. RESULTS: After a single o ral dose of 50 mg naftopidil test capsules or reference tablets, the main pharma cokinetic parameters AUC 0-24 : 295.6 ? 90.9 and 291.6 ? 89.3 ?g?L -1 ?h -1 ; AUC 0-∞ : 320.0 ? 97.2 and 318.0 ? 98.3 ?g?L -1 ?h -1 ; T max : 0.6 ? 0.2 and 0 .6 ? 0.2 h ; C max : 129.1 ? 60.7 and 138.3 ? 72.5 ?g? L -1 ; T 1/2 : 5.9 ? 1.7 and 6.4 ? 2.1 h , respectively. The relative bioavailability F 0-24 ,F 0-∞ were 101.9 ? 12.9 % and 101.2 ? 12.3 %, respectively. CONCLUSION: No signifi cant difference exists among the pharmacokinetic parameters for the test capsule s and the reference tablets of naftopidil. The two formulations were bioequivale nt.

Objectives: To study the protective effects of Nao Mai Tong(NMT) on middle cerebral artery occlusion(MCAO) induced focal brain ischemia reperfusion injury in rats. Methods: After rats were respectively given NMT 1 g/kg, 3 g/kg, 9 g/kg ig everyday for 1 week, the effects of NMT on the histological changes and behavior disorder caused by focal brain ischemia reperfusion which was made by occlusion of middle cerebral artery were investigated. The gasping time after the cutting of the head in ischemia reperfusion rat was recorded. The contents of ATP and LA were determined by radioimmunoassay. Results: NMT significantly reduced the extent of behavior disorder, descended the rate of cerebral infarction area, and improved histological injury of brain tissues. The grasping time after head cutting was prolonged. It was found that the level of ATP was increased and LA was decreased markedly. Conclusions: NMT shows a significant protective effect on histological, behavior and energy metabolic consequences of MCAO induced focal brain ischemia reperfusion injury.

Objectives:To study the pharmacokinetics and relative bioavailability of glipizide in healthy male volunteers. Methods:The glipizide concentrations in plasma were determined by HPLC UV. The column: Lichrospher C18 (5 ?m,150 mm?4.6 mm),the mobile phase: methanl∶0.01 mol/L sodium acetale buffer (pH 4.8) (59 ∶41); the flow rate:1 ml/min, the detection wavelength: 225 nm. The test and reference formulations of glipizide were given to 20 healthy male volunteers. Results: The calibration curve was linear within the range of (25～1 000)?g/L, r =0.999 4. The minimum detection limit was 25 ?g/L. The mean recovery was 89.84%, CV of inter day and intra day were no more than 5%.After a single oral dose of 10 mg glipizide test or reference tablet, the main pharmacokinetic parameters AUC 0-15, AUC 0-∞, T max ,C max and t 1/2 were (3 502.78?635.82) , (3 214.23?590.46)?g/( L?h),(3 868.22?699.93), (3 593.94?638.60)?g/(L?h),(3.85?1.44), (3.76?1.13)h, (550.80?110.19), (531.15?148.42)?g/L,(3.57?1.11)h and (3.80?1.06)h ,respectively. The relative bioavailability F 0-15 ,F 0-∞ were (110.6?19.8)% and (108.8?17.9)%. Conclusions: No significant difference exists among the pharmacokinetic parameters for the experimental tablets and the reference. The two formulations were bioequivalent.