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OBJECTIVE To estab lish the pre paration method of clopidogrel active thiol metabolite （CATM），and to provide reference for the synthesis of cis-CATM. METHODS CATM was prepared ，separated and purified with isolated rat liver perfusion and ChromCore 120 C18 preparative column ，using（S）-2-oxo-clopidogrel as substrate. The target compounds were identified by mass spectrometry and nuclear magnetic resonance spectroscopy. The retention time of the active configuration of CATM in the human body （cis-CATM）were compared to confirm the proportion of active configuration in the target product. RESULTS The conversion rate of the target product was 11.71％. The target products were identified as CATM by MS and 1H-NMR. Peak 2-peak 5 of CATM were four stereoisomers. The retention time of them were 21.3，22.3，26.5，27.3 min. The peak area ratios of them were 7.13％，7.23％，63.52％，14.97％，respectively. Based on that retention time of the active configuration of CATM in human body was 26.3 min，the active cis-stereoisomer in the target product CATM accounted for 63.52％. CONCLUSIONS This method is low-cost ，simple，and can prepare CATM with higher active configuration.
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Clopidogrel is the most commonly used antiplatelet agent for acute coronary syndrome, ischemic stroke, and before and after percutaneous coronary intervention, and endovascular treatment of large vessel occlusive stroke, but there are individual differences in antiplatelet effect, that is, clopidogrel resistance (CR). CR is usually attributed to the decrease of the concentration of sulfhydryl metabolites in plasma, and there are many factors that cause the decrease of the concentration of sulfhydryl metabolites. This article reviews the research progress of CR-related risk factors, so that clinicians can assess the risk of CR and adopt individualized antiplatelet therapy to improve the clinical outcome of patients.
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OBJECTIVE：To analyze the situation of inpatients with heart failure taking sacubitril-valsartan. METHODS ：The data of heart failture inpatients using sacubitril-valsartan in our hospital were collected during Oct. 2019 to Mar. 2020，including basic information of patients such as gender ，age，inpatient department ，length of stay ；the application of sacubitril-valsartan ， including indications ，contraindications，usage and dosage ，course of medication ；conversion with angiotensin converting enzyme inhibitor（ACEI）/angiotensin Ⅱ receptor antagonist （ARB）and adverse drug reactions ，were summarized. RESULTS ：A total of 252 cases were collected ，including 172 males（68.25％）and 80 females（31.75％）. The average age of the patients was （67.02± 14.23）years old ，and 85 cases were 75 years or older （33.73％）. Average hospitalization time was （12.03±8.19）d，the average left ventricular ejection fraction （LVEF）before medication was （38.69±10.45）％，the average blood potassium was （4.16±0.65） mmol/L，and the average estimated value of glomerular filtration （eGFR）was（69.14±32.01）mL/（min·1.73 m2）. The main distri- bution departments were cardiology department （59.14％），followed by nephrology department （8.73％），respiration department （7.14％），cardiac surgery department （5.95％），geriatrics department （5.56％），emergency medicine department （3.57％）and neurology department （3.17％）. All patients had indications ，but 25 cases（9.92％）had contraindications ，6 cases（2.38％）had blood potassium ＞5.4 mmol/L，19 cases（7.54％）had eGFR ＜15 mL/（min·1.73 m2）. The usage and dosage was 50 mg/bid （45.24％）；39 cases（15.47％）were given medicine once a day ，which was unreasonable. Average treatment course was （7.80± 5.86）d. 7 patients（2.78％）converted to ACEI ，and 3 patients（42.86％）had a conversion interval less than 36 h；20 patients （7.93％） were converted to ARB ，and there was no obvious inappropriate conversion. Hypotension occurred in 14 patients （5.56％）. Blood pressure returned to the normal range in 2 patients after drug withdrawal and 12 patients after dose reduction. No patient had adverse reactions such as involuntary muscle tremor and arrhythmia. CONCLUSIONS ： All the inpatients wit h heart failure in our hospital have indications and good safety. Only a few patients have blood pressure intolerance. However ，there were problems such as low dosage ，inappropriate frequency of administration ，drug use against contraindications，and inappropriate timing of drug conversion. Clinical pharmacists can carry out the knowledge propaganda of rational drug use ，strengthen the pharmaceutical care of patients ，timely detect the situation of irrational drug use and monitor adverse drug reactions ，and actively intervene to ensure the rationality and safety of patients ’medication.
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OBJECTIVE:To investigate the in vitro dissolution behavior and in vivo pharmacokinetics of Cinacalcet hydrochloride tablets, and to evaluate its in vivo-in vitro correlation (IVIVC). METHODS:HPLC method was adopted to determine the accumulative dissolution(Q) of Cinacalcet hydrochloride tablets in 8 kinds of medium [pH 1.2 hydrochloric acid solution,pH 2.0 hydrochloric acid solution,pH 4.5 acetate buffer solution,pH 6.8 phosphate buffer solution,water,artificial gastric fluid(SGF),full belly artificial intestinal fluid(FeSSIF),fasting artificial intestinal fluid(FaSSIF)],and the dissolution curves were drawn. HPLC-MS method was used to determine the blood concentrations of Cinacalcet hydrochloride tablets. A total of 12 healthy male volunteers were selected and given single oral dose of Cinacalcet hydrochloride tablets 75 mg under the state of fasting or satiety(high-fat food). The blood concentration of cinacalcet hydrochlorid was determined before medication(0 h)and 0.5,1,2,3,4,6,8,12,24 h after medication. Average blood concentration-time curves were drawn. The in vivo accumulative absorption percentage (F) of satiety group was calculated by using DAS 3.0 software. Linear regression of F with in vitro Q was carried out to analyze its IVIVC. RESULTS:There was great difference among dissolution curves of Cinacalcet hydrochloride tablets in 8 kinds of dissolution mediums. There were differences of AUC0→t,AUC0→∞ and cmax between fasting group and satiety group,with statistical significance(P＜0.05),showing high-fat food had significant effect on in vivo pharmacokinetics. Correlation coefficient of in vivo F in satiety group with in vitro Q of the tablets in FeSSIF was highest (0.977 9),manifesting good IVIVC (class A). CONCLUSIONS:The in vitro dissolution behavior of Cinacalcet hydrochloride tablets in FeSSIF(paddle method,50 r/min)is well associated with its in vivo pharmacokinetics,which can be used for predicting in vivo dissolution and absorption of the tablets.
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Objective To explore the curative effects of pulmonary surfactant (PS) injected via venous indwelling needle instead of the endotracheal tube combined with continuous positive airway pressure(CPAP) in the treatment of premature infants with neonatal respiratory distress syndrome (NRDS).Methods 28 premature infants with NRDS were selected,12 cases with gestational age of 28-31 weeks,16 cases with gestational age of 32-34 weeks,and all the cases were treated with PS injected via venous indwelling needle combined with CPAP.The changes in clinical symptoms,blood gas analysis,oxygen saturation,and the parameters of CPAP after treatment were observed.The tracheal intubation in 72h,the second use of PS,respiratory support duration,hospital duration,and the complications between the MIST treatment group and INSURE treatment group were compared.Results There were significant differences in changes of clinical symptoms,percutaneous oxygen saturation,pH,partial pressure of oxyge,partial pressure of carbon dioxide,fraction of inspiration O2 and (positive end expiratory pressure) PEEP after treatment(all P ＜ 0.05).There were statistically significant differences in tracheal intubation in 72h,the second use of PS,complications and respiratory support duration between the MIST group and INSURE group (all P ＜ 0.05).There were no statistically significant differences in bronchopulmonary dysplasia,ROP,PDA,intracranial hemorrhage,and hospital duration (all P ＞ 0.05).Conclusion The therapy of PS injected via venous indwelling needle combined with CPAP in the treatment of premature infants is effective.The method MIST is simple and convenient,has less injury to premature infants,and can reduce frequency and dosage of the PS and respiratory support time.
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Objective:To analyze one case of unreasonable drug use to promote reasonable drug use in clinics. Methods: The treatment regimen with irrational drug use for one case of type 2 diabetes with complicated urinary tract infection were analyzed, and the reasons for the irrationality were summarized and some suggestions for avoiding unreasonable drug use were put forward. Results:The choice of moxifloxacin in the initial treatment was irrational, and no combination indications were shown. Clinical pharmacists partici-pated in the ward rounds and timely communicated with the clinicians to correct the drug use. Conclusion:Due to the drug resistance, pharmacokinetic characteristics and adverse reactions, moxifloxacin is unsuitable for the anti-infection treatment of complicated urinary tract infection. Clinical pharmacists should provide individualized treatment for patients to improve the effectiveness of drug therapy.
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Objective:To analyze one case of unreasonable drug use to promote reasonable drug use in clinics. Methods: The treatment regimen with irrational drug use for one case of type 2 diabetes with complicated urinary tract infection were analyzed, and the reasons for the irrationality were summarized and some suggestions for avoiding unreasonable drug use were put forward. Results:The choice of moxifloxacin in the initial treatment was irrational, and no combination indications were shown. Clinical pharmacists partici-pated in the ward rounds and timely communicated with the clinicians to correct the drug use. Conclusion:Due to the drug resistance, pharmacokinetic characteristics and adverse reactions, moxifloxacin is unsuitable for the anti-infection treatment of complicated urinary tract infection. Clinical pharmacists should provide individualized treatment for patients to improve the effectiveness of drug therapy.
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Objective To investigate the clinical features and drug resistance of neonatal purulent meningitis caused by Escherichia coli. Methods The clinical data of 46 neonates diagnosed with purulent meningitis caused by Escherichia coli were retrospectively analyzed from June 2004 to June 2014. The neonates were divided into community acquired infection group and nosocomial infection group, or early group (from June 2004 to May 2009) and late group (from 2009 June to June 2014). Result Fever, hypothermia, lethargy, poor feeding, tachypnea, and tachycardia were common clinical manifestations in all neonates. The detection rate of ESBLs was signiifcantly higher in nosocomial infection group than that in community acquired infection group (P?
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OBJECTIVE:To establish the method for the simultaneous determination of clopidogrel (CLO) and its active metabolites (CATM) and inactive metabolites (CCAM),and to conduct pharmacokinetic study. METHODS:The plasma sam-ple had been derivatized by 2-bromine-3′-methoxy acetophenone(MPB),and was precipitated by acetonitrile. Using carbam-azepine as internal standard,UPLC-MS/MS was adopted. The separation was performed on Waters ACQUITY UPLC HSS T3 column with mobile phase consisted of water(containing 0.1% formic acid)-acetonitrile(containing 0.1% formic acid)using a gradient elution program at the flow rate of 0.50 ml/min. The ESI was equipped and quantitative analysis was operated in posi-tive ion and MRM mode. The mass transition ion-pairs were followed as m/z 322.1→211.8(CLO),m/z 504.1→155.0(the alkyl-ation derivatives of CATM,CATMD),m/z 308.3→198.0(CCAM),m/z 273.2→194.3(internal standard). RESULTS:The lin-ear calibration curves for CLO,CATMD and CCAM were obtained in the concentration range of 0.03-20.00 ng/ml,0.30-200.00 ng/ml and 10.00-10 000.00 ng/ml in plasma,respectively;intra-day and inter-day RSD for them were all less than 15%,and relative error(RE)ranged from -3.5% to 5.7%. Main pharmacokinetic parameters of CLO,CATMD and CCAM in 5 healthy volunteers after oral administration of CLO 300 mg were as follows:cmax were(7.89±5.46),(15.58±8.08),(8 023.33± 1 047.39)ng/ml;tmax were(1.25 ± 0.43),(1.25 ± 0.43),(1.67 ± 0.29)h;t1/2 were (2.31 ± 0.61),(0.64 ± 0.08),(6.53 ± 2.55)h;AUC0-t were(17.19±14.59),(21.39±9.58),(30 648.85±8 026.63)ng·h/ml. CONCLUSIONS:The established method is sensi-tive,rapid and convenient,which is suitable for pharmacokinetic study and plasma concentration determination of CLO and its metabolites.
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OBJECTIVE To investigate the distribution and resistance of commonly encountered pathogens,and provide reference of antimicrobial agents.METHODS For the clinical specimens during the last three years,flora identification and bacteriostatic test were operated with Microscan WalkAway-40.RESULTS Gram-negative bacteria were 252,507 and 742 strains,Gram-positive bacteria were 142,166,and 243 strains,fung were 0,26,and 229 strains from 2002 to 2004,respectively,the most commonly encountered Gram-negative bacteria were Escherichia coli,Klebsiella pneumoniae,Pseudomonas aeruginosa,Enterobacter cloacae,and Acinetobacter baumannii;the Gram positive bacteria were Staphylococcus aureus,S.epidermidis,S.haemolyticus,and Enterococcus.CONCLUSIONS It is important for reasonable drug application to know the distribution and resistance of commonly encountered bacteria.
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OBJECTIVE:To observe the factors that influence the fluctuation of serum concentrations of valproic acid and to improve the effectiveness and usefulness of monitoring the serum concentration.METHODS:The factors that influence the serum concentration of valproic acid were summed up and the countermeasures were put forward.RESULTS:These influencing factors included the drug administration time;the blood sampling time;the right moment for monitoring;the dosage forms and quality of drug;the obedience of patient;combining use of drugs and the physiological and pathological conditions of pa?tients.CONCLUSION:When epileptic patients receive long-term medical treatment,the doctor,the patient and the pharma?cist should communicate mutually,establish the relevant data,pay attention to those factors and ensure the patients safe and effective in use of drug.