Determination of Fluconazole in Human Plasma by UPLC-MS/MS with Isotopes Dilution / 中国药房

OBJECTIVE： To establish a method for determination of fluconazole concentration in human plasma. METHODS： UPLC-MS/MS method was adopted to determine plasma after precipitated with acetonitrile. Using isotope fluconazole-d4 as internal standard， the determination was performed on ACQUITY UPLC BEH C18 column with mobile phase consisted of 0.1％ formic acid-acetonitrile （gradient elution） at the flow rate of 0.3 mL/min. The column temperature was 40 ℃， and the sample size was 3 μL. ESI was used for positive ion scanning by multiple reaction monitoring mode. The ion pairs for quantitative analysis were m/z 307.1→220.0 （fluconazole） and m/z 311.1→223.0 （internal standard）. RESULTS： The linear range of fluconazole was 10-5 000 ng/mL （r＝0.998 1）. The limits of quantitation was 10 ng/mL. RSDs of intra-day and inter-day were less than 8％； accuracy ranged 95.8％-106.7％. The extraction recovery ranged 97.3％-107.3％ （RSD＜5.0％， n＝6）， and matrix effect， dilution effect and residual effect didn’t influence quantitative analysis of the substance to be measured. CONCLUSIONS： The method is simple， rapid， specific and accurate， which can be used for therapeutic drug monitoring and pharmacokinetic study of fluconazole.

Extended thymectomy by subxiphoid approach video-assisted thoracoscopic surgery(VATS) for myasthenia gravis:clinical analysis of 64 cases / 中华胸心血管外科杂志

To investigate the clinical efficacy of extended thymectomy by subxiphoid approach video-assisted thoracoscopic surgery(VATS) for myasthenia gravis. Methods We retrospectively analyzed the clinical date of 64 cases of myasthenia gravis treated by subxiphoid approach VATS in the same surgical team from September 2015 to April 2018. The patients were equally divided into 4 groups(A, B, C and D) according to the date of operation. Comparisons were made among the four groups in operation time, blood loss during operation, rate of conversion to thoracotomy, postoperative complications, postoperative hospital stay, duration and amount of postoperative chest tube drainage, frequenlly of surgery. The operative effect of different stage was analyzed. Results There were no intraoperative deaths. 1 patient(group A) was converted to thoracotomy. 3 patients(2 cases of group A; 1 case of group D) had lung infection. 1 patient(group B) developed myasthenia crisis after surgery, and the rest patients showed obvious improvement in postoperative myasthenia symptoms. No significant differences were found in postoperative complications, rate of conversion to thoracotomy, postoperative hospital stay, duration and amount of postoperative chest tube drainage among the 4 groups(P >0. 05). The operation time was significantly longer in group A(186. 25 ± 25. 79) min than the other 3 groups [B(128. 75 ± 16. 28) min, C(135. 00 ± 21. 29) min, D(128. 75 ± 19. 62)min], P <0. 05. The blood loss in surgery was significsntly more in group A(110. 00 ±38. 82)ml than that in the other 3 groups[B(63. 75 ±28. 26)ml, C(58. 13 ±27. 86)ml, D(58. 75 ±25. 00)ml], P <0. 05, while no statistical difference was found among group B, C and D. The frequency of surgery was increased from 1. 6 cases in group A to 2. 3, 2. 7 and 2. 7 cases one month in B, C and D, respectively. Conclusion The results of the present study have shown that subxiphoid approach VATS thymectomy is safe and feasible for the treatment of MG patients. For thoracic surgeons with certain experience in thoracoscopic technique, a plateau of the surgical skill of the subxiphoid opproach can be reached after learning curve procedures.

Investigation and Analysis of Metabolic Drug Interaction in Outpatient Prescriptions of Hypertension Pa-tients / 中国药房

OBJECTIVE:To investigate drug combination in outpatient prescriptions of hypertension patients in our hospital, provide reference for rational drug use in clinic. METHODS:The outpatient prescriptions of patients diagnosed as hypertension dur-ing Jan. 1st to Feb. 1st in 2015 were collected from the hospital. The prescriptions of two or more than two drugs were screened, and the prescriptions of drug combination containing CYP enzyme substrate,inhibitor or inducer were recorded. Guided by metabol-ic enzymology theory,the potential metabolic drug interactions in prescriptions were evaluated on the basis of relevant literature and data reports. RESULTS:Totally 1042 prescriptions were consulted. The prescriptions of the combined medication were 551, and the potential metabolic drug-drug interactions were detected at 249 prescriptions,accounting for 45.2％. Main CYP enzyme sub-types were CYP3A4,CYP2C9,CYP2C19 and CYP2D6. Totally 214 prescriptions were correlated with CYP3A4,accounting for 85.9％ of drug interaction prescriptions;CYP3A4 substrate combined with substrate in 199 prescriptions,with inhibitor in 27 pre-scriptions,and with inducer in 11 prescriptions. Totally 27 prescriptions were correlated with CYP2C9,accounting for 10.8％ of drug interaction prescriptions;CYP2C9 substrate combined with substrate in 8 prescriptions,and with inhibitor in 20 prescriptions. Totally 27 prescriptions were correlated with CYP2D6,accounting for 10.8％ of drug interaction prescriptions;CYP2D6 substrate combined with substrate in 15 prescriptions,and with inhibitor in 12 prescriptions. Totally 4 prescriptions were correlated with CYP2C19,accounting for 1.6％ of drug interaction prescriptions;CYP2C9 substrate combined with inhibitor in 2 prescriptions, and with inducer in 2 prescriptions. CONCLUSIONS:Many metabolic drug-drug interactions are detected in the outpatient prescrip-tions of hypertension patients in our hospital. In order to improve the rationality and safety of the prescription,clinicians and phar-macists should pay attention to the drug combinations with drug-drug interactions which have been reported in the existing litera-ture,and choose similar drugs without or with little interactions.

Effect of aprepitant on pharmacokinetics of cancer chemotherapy patients with oral oxycodone controlled release tablets / 中国生化药物杂志

Objective To investigate effect of the mild CYP3A4 inhibitor aprepitant on the pharmacokinetics of orally administered controlled-release ( CR) oxycodone.Methods This study designed was an single-sequence with two phases in cancer patients with pain who continued to be administered orally with multiple doses of CR oxycodone every 8 or 12 hours.Plasma concentration of oxycodone and its metabolites were measured up to 8 hours after administration as follows: on day 1, CR oxycodone was administered alone; on day 2, CR oxycodone was administered with aprepitant (125 mg, at the same time of oxycodone dosing in the morning).The steady-state trough concentrations ( Css) were measured from day 1 to day 3.Results Aprepitant increased the area under the plasma concentration-time curve (AUC0-8) of oxycodone by 25%(P<0.001) and of oxymorphone by 34% (P<0.001), as well as decreased the AUC0-8 of noroxycodone by 14% (P<0.001).Moreover, aprepitant increased Css of oxycodone by 57%(P=0.001) and of oxymorphone by 36% (P <0.001) and decreased Css of noroxycodone by 24% (P =0.02) at day 3 compared to day 1.Conclusion The clinical use of aprepitant in patients receiving multiple doses of CR oxycodone for cancer pain significantly altered plasma concentration levels, but would not appear to need modification of the CR oxycodone dose.

The diagnostic value of multichannel intraluminal esophageal impedance and pH monitoring in gastroesophageal reflux-related cough / 中华内科杂志

Objective To evaluate the diagnostic value and limitation of multichannel intraluminal esophageal impedance and pH (MII-pH) monitoring on the diagnosis of gastroesophageal reflux-related chronic cough (GERC).Methods The patients with suspicious GERC consecutively referred to our respiratory clinic between May 2010 and July 2011 underwent a MII-pH monitoring,and received anti-reflux drug therapy,irrespective of the laboratory findings.Chronic cough due to gastroesophageal reflux was determined when there was a favorable response to anti-reflux therapy.Then,the sensitivity,specificity,false positive and negative rate,total consistence,positively and negatively predictive value,the area under the curve of ROC and the Kappa value of the laboratory investigation were calculated for the diagnosis of GERC.Results During the research period,56 patients completed MII-pH monitoring.Among them,the abnormal reflux was found in 35 patients,and GERC was finally confirmed in 30 patients (85.7％) including 25 patients (83.3％) due to acid reflux and 5 patients (16.7％) due to non-acid reflux.In the remaining 21 patients with normal reflux episodes,6 patients (28.6％) could be explained by non-acid reflux for their cough because of a relatively predominant weakly acid reflux and favorable response to empirical anti-reflux therapy.For the diagnosis of GERC,MII-pH monitoring had the sensitivity of 83.3％,the specificity of 75.0％,false positive rate of 25.0％,false negative rate of 16.7％,total consistence of 80.4％,positive predictive value of 85.7％,negative predictive value of 71.4％,the area under the curve of ROC of 0.792 and Kappa value of 0.577 respectively.Conclusion MII-pH is a sensitive and reliable tool for the diagnosis of GERC due to its ability to detect both acid and non-acid reflux.

Validation of the reliability and clinical value of the simplified cough score / 中华全科医师杂志

Objective To validate the repeatability of the simplified cough score and its responsiveness to effective treatment and investigate the relationship between the simplified cough score and cough symptom score.MethodsA total of 119 patients with chronic cough referred to our respiratory clinic were recruited into the study between June 2010 and February 2011. Cough severity was evaluated by the simplified cough score,cough symptom score,Leicester cough questionnaire,and cough reflex sensitivity detection,and the correlations among them were analyzed.The change ratio,effect size,and standardized response mean of the simplified cough score were calculated after a 2-week course of effective treatment.The repeatability of the simplified cough score was assessed in 99 untreated patients with stable chronic cough.ResultsThe intraclass correlation coefficient in a 3-day test-retest interval of simplified cough score was 0.90 ( 95 ％ CI =0.84 - 0.92,P =0.00 ) for daytime and 0.89 ( 95 ％ CI =0.91 - 0.96,P =0.00 ) for nighttime. There was an obvious positive linear correlation between the simplified cough score and cough symptom score ( daytime:r =0.82,P =0.00 ; nighttime:r =0.92,P =0.00 ),a significant negative linear correlation between the cough score and Leicester cough questionnaire,and a weak but significant negative correlation between the simplified cough score and cough threshold C2 or C5 to capsaicin. After a 2-week course of effective treatment,the change ratio,effect size,and standardized response mean were 46.71％,1.16,and 1.05 for daytime and 71.87％,1.09,and 1.10 for nighttime,respectively.ConclusionThe simplified cough score is a reliable and valid tool for evaluation of cough severity in clinical practice.

Pharmacokinetics of arbidol capsule in Chinese healthy volunteers / 中国新药与临床杂志

AIM To study the pharmacokinetics of arbidol capsule in Chinese healthy volunteers.METHODS A single oral dose of arbidol capsule 200 mg was given to 20 healthy volunteers respectively.Plasma samples were prepared based on a simple liquid-liquid extraction.The extracted samples were analyzed by HPLC equipped with UV detection.Pharmacokinetic parameters were calculated by 3P87 software. RESULTS The main pharmacokinetic parameters of arbidol were as follows:c(max)(418±s 241)μg·L-1,t(max)(1.3±1.2)h,t(1/2α)(1.9±2.3)h,t1/2β(14±5),hAU0-t(2 633±1 071)μg·L-1,Vc/F(0.7±0.6)L,CL(0.08±0.03)L·h-1,CONLUSION The pharmacokinetics of arbidol capsule in human body accord with two-compartmetn open model.The study will offer the pharmacokinetic parameters for the clinical application of arbidol.

Value of Mycobacterial Interspersed Repetitive Unit on Tuberculosis Outbreak in Prison / 中华医院感染学杂志

OBJECTIVE To explore the value of molecular epidemic technology on tuberculosis outbreak in prison.METHODS Using mycobacterial interspersed repetitive unit(MIRU) genotyping to discriminate and recognize 7 strains on tuberculosis cases.RESULTS Among 7 Mycobacterium tuberculosis isolates,6 strains′ MIRU genotyping was 233325153533,another one was 242325152322.Six M.tuberculosis cases were infected by the same MIRU genotyping tuberculosis strains,but another one was not.CONCLUSIONS MIRU genotyping to discriminate and track source of infection is possible.