1.Clinical research of the effect of dexmedetomidine on patients undergoing abdomi-nal surgery and on quality of post-surgery recovery
The Chinese Journal of Clinical Pharmacology 2014;(4):317-319
Objective To evaluate the clinical efficacy and safety of dexmedetomidine ( DEX ) on patients undergoing abdominal surgery who received general anesthesia and on quality of post -surgery recovery.Methods Ninety-one patients who were planed for abdominal surgery with general anesthesia were randomly divided into treatment group ( n=44 ) and control group ( n=47 ) with random number table.Patients in control group were given saline 15 mL 15 min prior general anesthesia.And patients in treatment group were given DEX 0.5 μg· kg -1 and then 0.25 μg· kg -1 · h-1 in the procedure of operation.Spontaneous breath-ing, awaking time, extubation time and side effects were compared be-tween two groups.Results The VRS analgesic score in treatment group was much lower than that in control ( P<0.05 ).The incidence rate of agitation bucking in treatment group was much lower than that in control group ( P<0.05 ).But spontaneous breathing time , awaking time and extubation time showed no statistical difference between the two groups ( P>0.05).Conclusion DEX can significantly reduce the risk of de-veloping agitation , bucking and improve the general anesthesia efficacy in patients receiving abdominal surgery who underwent general anesthesia.
2.Study on pharmacokinetics of cefotetan disodium in Chinese healthy volunteers
Su-Xia XIA ; Si TANG ; Shi-Liang ZHANG ; Xiao-Qian DONG ; Rui YANG ; Yue-Min WANG
The Chinese Journal of Clinical Pharmacology 2014;(4):320-323
Objective To study the pharmacokinetics of cefotetan diso-dium injection in Chinese healthy volunteers.Methods The study was designed as an open , randomized , parallel and single-dose single cycle study.Thirty healthy volunteers were divided into three groups.Each group included five volunteers male and five female volunteers.The vol-unteers in different groups were administered with single dose of 0.5 , 1.0 or 2.0 g cefotetan disodium , respectively.Plasma concentrations of cefotetan disodium were determined by LC -MS/MS method.The phar-macokinetic parameters of cefotetan disodium were calculated by DAS version 2.1 software.Results The main pharmacokinetic parameters of three doses (0.5, 1.0, 2.0 g)of cefotetan disodium were as follows:cmax were(65.25 ±19.84), (118.06 ±20.54), (231.24 ±66.75)mg· L-1;tmax were(0.99 ±0.09), (0.98 ±0.08), (0.97 ±0.12)h; t1/2 were(4.44 ±0.72 ), (3.93 ±0.46 ), (4.18 ±0.73 ) h; AUC0-t were ( 263.58 ± 63.81 ) , ( 421.93 ± 48.87 ) , ( 896.99 ± 249.78 ) mg· L-1 · h -1 , respectively.Urinary recovery rate within 24 h was (65.62 ±10.23 )%.Conclusion The plasma concentration - time curve fits two compartment model.The safe dose was 0.5-2.0 g.
3.Effects of the genetic polymorphism CYP2 C19 on pharmacokinetics of citalopram in Chinese healthy volunteers
The Chinese Journal of Clinical Pharmacology 2014;(4):324-326,331
Objective To investigate the effets of cytochrome CYP2C19 gene polymorphism on the pharmacokinetics of citalopram in Chinese healthy male volunteers.Methods Twenty-four Chinese healthy male volunteers were orally administered with a single dose of citalopram 20 mg.The venous blood samples were collected , using anticoagulantion EDTA to extract DNA, and the genotype was detected .The blood sam-ples(5 mL) from the bolunteers were collected before and after the ad-ministration of citalopram and plasma was taken .The plasma concentra-tion of citalopram was examined by HPLC -MS/MS method .The geno-type CYP2 C19 was measured by PCR -based sequencing.The measure-ments were performed by HPLC -MS/MS.Pharmacokinetic differences of citalopram on patients with different genotypes were compared .Results Two out of 24 volunteers were poor metabolizing genotype ( PM ) , and 22 were extensive metabolizers (EM).Among the EM 12 were homozy-gotes and 10 were heterozygotes.The pharmacokinetic of citalopram was largely influenced by CYP2 C19 genetic polymorphism , and also effected by the volunteers′age and weight.Conclusion The CYP2 C19 genotype of patients should be detected before the clinical appliaction of citalo-pram, and the age as well as weight also need to be considered .
4.Detection of 16 S rRNA methylase genes in clinical isolates carbapenem-resistant Klebsiella-pneumoniae
Ya-Ping HANG ; Chang-Xiu NING ; Hong WANG ; Qiao-Shi ZHONG ; Xiao-Yan HU ; Bai-Ling ZHANG ; Nan ZHANG ; Long-Hua HU
The Chinese Journal of Clinical Pharmacology 2014;(4):327-331
Objective To investigate existence and homology of 16 S rRNA methylase genes in carbapenem -resistant Klebsiella-pneumoniae ( CRKP ) clinical isolates.Methods Twenty -nine CRKPs were col-lected from four hospitals in Nanchang.PCR amplifications of drug resist-ant genes were performed.The horizontal transmission of the resistance plasmids was evaluated by conjugation and homology of the isolates was analyzed by pulsed field gel electrophoresis ( PFGE).Results Resistant rates of twenty -nine clinical isolates to amikacin and gentamicin were 37.9%( 11/29 ) and 69.0%( 20/29 ) , respectively.The amikacin re-sistanted isolates were simultaneously resistant to gentamicin.The exist-ence of 16 S rRNA methylase positive genes were detected in 10 isolates , including 9 strains carrying armA genes,1 strain carrying rmtB gene.All the 10 strains with 16 S rRNA methylase positive genes harbored β-lac-tamase genes and 7 strains also harbored carbapenemase genes , with blaKPC-2 and blaNDM-1 being the main genotypes.Ten experimental strains were successfully typed by PFGE and classified into 9 different genotypes and resistance plasmids were successfully transferred into the recipient E.coli J53 through conjugation experiments of 3 armA -positive isolates. Conclusion The 16S rRNA methylase gene is highly relevant to carbapenem -resistant klebsiella -pneumoniae in terms of resistance to aminoglycosides , and armA is the main genotype.Plasmids carried 16 S rRNA methylase gene can be horizontally disseminated.
5.Susceptibility and molecular mechanism of carbapenem -resistant Acinetobacter baumannii
The Chinese Journal of Clinical Pharmacology 2014;(4):332-336
Objective To investigate the susceptibility of antimicrobial agents, carbapenemase genotypes and clonal relatedness among carbap-enem-resistant Acinetobacter baumannii ( CRAB) isolated from intensive care unit ( ICU) in Shenzhen People′s Hospital.Methods Forty-eight non-duplicated CRAB isolates were collected from ICU in this hospital in 2010.The minimum inhibitory concentrations ( MICs) of fifteen anti-microbial agents against CRAB were detected by agar dilution method.Polymerase chain reaction ( PCR) and DNA sequencing were used to in-vestigate the carbapenemase genotype among CRAB.All isolates were typed by pulse field gel electrophoresis ( PFGE ).Results Polymixin B showed the highest activity against forty-eight CRAB isolates ( suscepti-bility of 100%) , with the MIC50/MIC90 of 1 μg· mL -1 , followed by mi-nocycline (susceptibility of 95.8%), with the MIC50/MIC90 of 4 μg· mL -1, and tigecycline (intermediate of 89.6%), with the MIC50/MIC90 of 4 μg· mL-1 , respectively.Approximately ninety percent (43/48 ) of CRAB isolates harbored blaOXA-23-like , which showed high resistance to imipenem and meropenem , with the main distribution of MICs ranging from 16 to 64 μg · mL-1.Three and two CRAB isolates harbored blaOXA-58-like and ISAba1-blaOXA-51-like, respectively.Both of them exhibited intermediate resistance against imipenem and meropenem, with the main distribution of MICs ranging from 8 to 16 μg· mL-1.blaOXA-24-like, blaOXA-143-like, metallo-β-lactamase and KPC genes were not detected in any of isolates.Four distinct PFGE patterns were observed among forty-eight isolates of CRAB.All of type A isolates harbored blaOXA-23-like , accounting for 87.5%(42/48) of CRAB.Conclusion The spread of CRAB clone harboring blaOXA-23-like occurred in ICU of our hospital during 2010.
6.Effect of the combination of anisodamine and fentanyl post-processing against my-ocardial ischemia and reperfusion injury on metabolic indicators of rabbits
Wen-Ting ZHANG ; Fang-Jiang LI ; Xiao-Yuan WANG ; Qing LI ; Qiang ZHANG ; Hui-Xian LI
The Chinese Journal of Clinical Pharmacology 2014;(4):337-339
Objective To explore the effect of the combination of aniso-damine and fentanyl on metabolic indicators , as well as the two drugs separately combined with myocardial ischemia post -processing against myocardial ischemia and reperfusion injury in rabbits.Methods The pre-ligated left anterior descending coronary artery ( LAD) for 30 min and 120 min of reperfusion were adopted to establish myocardial ischemia-reperfusion model.The 48 Japanese white rabbits were randomly as-signed to six groups ( n=8 each ): Sham-operated group ( group S ) , to separate LAD without ligation; ischemia -reperfusion group ( group I/R ) , to restore reperfusion directly; ischemic postconditioning group ( group IP C ) after 30 min′s ischemia , to give ischemic postconditioning and then to restore reperfusion; fentanyl postconditioning group ( group F), anisodamine postconditioning group ( group A), and a combination of fentanyl and anisodamine postconditioning group ( group F+A):ische-mia for 28 min, and then different doses were injected respectively through ear marginal vein as follows: 5 μg · kg -1 of fentanyl , 5 mg · kg -1 of anisodamine , and the two kind of drugs combined for pharmanic post-processing.After 30 min of ischemia , post conditioning was given and then reperfusion was restrored.Differences in the peripheral metabo-lism of superoxide dismutase ( SOD ) , and malondialdehyde ( MDA ) were detected.Results The group A and group F were equal in the concentration of MDA and the active concentration of SOD ( P>0.05 ) ,but for the concentration of MDA , group F+A was lower than these two groups and group IP C was higher than them.However , in terms of the active concentration of SOD, group F+A was higher than these two groups and group IP C was lower than them (P<0.01) .Conclusion Myocardial ischemic postconditioning combined with fentanyl and anisodamine for the treatment of myocardial reperfu -sion injury was much more effective than the single -drug combination with ischemic postconditioning.
7.Tetramethylpyrazine inhibits neointimia formation induced by platelet -derived growth factor through suppressing inflammatory and adhesion molecular expression
Hong-Bing ZHANG ; Qiang LI ; Jing FENG ; Ke-Ping DI
The Chinese Journal of Clinical Pharmacology 2014;(4):340-343
Objective To investigate the effect of tetramethylpyrazine ( TMP) on neointimal hyperplasia induced by balloon injury.Methods VSMCs were cultured by tissue explants adherent method and VSMCs proliferation models induced by platelet -derived growth factor ( PDGF) were established.Cell counting analysis was adopted to evaluate the in-hibitory effects of TMP in a dose of 0, 20, 40 and 80 μmol · L-1 on VSMCs.Western blot analysis was performed to analyze the effect of TMP on the activator protein -1 ( AP-1 ) , proliferating cell nuclear antigen ( PCNA ) , cyclooxygenase ( COX-2 ) , intercellular adhesion molecular ( ICAM -1 ) , and integrin -linked kinase ( ILK ) expressions in VSMCs.Hemetoxylin and Eosin ( HE) staining was performed to investi-gate the effects of TMP on the neointimal hyperplasia induced by balloon injury.Results TMP inhibited cell proliferation induced by PDGF ( 20μg· L-1 ) in a dose-dependent (0, 20, 40, 80 μmol· L-1 ) manner.Remarkable decreases of AP -1, PCNA, COX-2, ICAM-1 and ILK expression were demonstrated in the TMP group compared with the model group in VSMCs.TMP inhibited the neointimal thickening induced by ballon injury , with a significantly lower ratio of intima -to-media area ( l/M) in the TMP group.Conclusion TMP plays a role in preventing neointimal hyperplasia through inhibiting or blocking proliferation , expressions of inflammatory genes and adhesion molecules.
8.Experimental study on the effect of pharmacodynamics of compound mometasone nasal spray on guinea pig with allergic rhinitis
The Chinese Journal of Clinical Pharmacology 2014;(4):344-346
Objective To investigate the effect of compound mometa-sone nasal spray on guinea pigs with allergic rhinitis.Methods Forty allergic rhinitis models were built by using 10%toluenediisocyanate olive oil intranasally , which were then divided into four groups randomly: the model group , the blank group , the test-single group and the test -com-bination group.The two test groups were given medicine ( bilateral nasal , with each side 40 μL) at the eighth day after sensitization and an hour before inspiration , respectively.The guinea pigs were administrated 5 consecutive days a week and then suspended the medicine for 2 days.The treatment lasted for 3 weeks.The other two groups were given 0.9%NaCl.The effects of the drug on syndrome score , the amount of eosino-phile granulocytes (EG), pathological changes and the content of nasal histamine were observed.Results The symptoms of allergic rhinitis , the pathological changes and the amount of EG were effectively inhibited or reduced by compound mometasone nasal spray.However , there was no obvious difference between test -combination and test -single groups in contents of histamine in mucosa.Conclusion Compound mometasone nasal spray has a better effect on treating allergic rhinitis in guinea pigs.
9.Effect of MDR1 gene polymorphism on the transportation of thiopurine and study on its possible mechanism
Yong HE ; Pan CHEN ; Xia ZHU ; Jing FENG ; Xue-Ding WANG ; Min HUANG
The Chinese Journal of Clinical Pharmacology 2014;(4):347-349,353
Objective The effect of MDR1 gene polymorphism on the difference in the transportation of thiopurine and its possible mechanism were explored.Methods The recombinant plasmids of wild -type and mutant haplotype of MDR1 were constructed and transfected into cells , the difference in the transportation of 6 -thiopurine in different MDR1 haplotype were studied and the MDR 1 protein expression were analyzed.Results The 6-thiopurine-efflux activity of MDR1 mutant haplotype was significantly weaker than that of MDR 1 wild-type haplotype ( P=0.014 ) , but no difference in protein expression of the two type MDR 1 was found ( P>0.05 ) , suggesting that the difference in the 6-thiopu-rine-efflux activity between MDR 1 wild-type and mutant haplotype can-not be explained by the difference in protein expression between the two MDR1 haplotypes.Conclusion The thiopurine-efflux activity varies in different MDR1 haplotypes , which maybe is one of the reasons for the in-terindividual variations in thiopurine response.The varied effects of the different MDR1 genotype on the drug transportation are not caused by the different protein expression of MDR 1, but by the difference in MDR1 protein folding and conformation leading to the change in the drug trans-portation activity.
10.Comparison of the cephalosporins and penicillins on the eradication of Helicobacter pylori by Meta-analysis
Can LI ; Yingying YAN ; Suodi ZHAI
The Chinese Journal of Clinical Pharmacology 2014;(4):350-353
Objective To compare the relative efficacy and safety of cephalosporins or penicillins based H.pylori eradication regimen.Meth-ods Electronic databases were searched to identify the randomized con-trolled trials ( RCTs ) comparing cephalosporins and penecillins for H.pylori eradication.The outcome measure was H.pylori eradication rate , incidence of adverse drug reactions ( ADR) and ulcer healing.Five stud-ies including 513 patients were identified.Results No statistical differ-ence on H.pylori eradication efficacy between cephalosporins and peni-cillins based regimen was shown on Meta -analysis ( P>0.05 ).No se-vere adverse drug reaction ( ADR) was reported in the identified studies , but the incidence of ADR of cephalosporins group was significantly lower than that of penicillin group ( P<0.01 ).Conclusion The efficacy of cephalosporins is similar to penicillins for H.pylori eradication , but cephalosporins have shown a significantly lower incidence of ADR.
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