Research Progress on Factors Affecting the Blood Concentration of Hydroxychloroquine / 医药导报

Originally used as an antimalarial drug,hydroxychloroquine is now widely used in the treatment of rheumatic immune diseases due to its cost-effectiveness,safety,and efficacy.In addition to its immunomodulatory effects,hydroxychloroquine also exhibits anti thrombotic,anti-hypolipidemic,and anti-hypoglycemic properties.Hydroxychloroquine blood levels are correlated with clinical outcomes and adverse reactions,and can reflect patient compliance.However,due to the complex pharmacokinetic profile of hydroxychloroquine,significant inter-individual differences in blood concentration exist even with the administration of the same dosage.This study investigates the factors affecting the blood concentration of hydroxychloroquine in terms of physiological factors,pathological factors,metabolic enzyme gene polymorphisms,and drug-related factors.The aim is to provide a reference for rational clinical use and the development of individualized dosing.

Simultaneous determination of bepotastine and hydroxychloroquine concentrations in human breast milk by LC-MS/MS / 中国药房

OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry （LC-MS/MS） method for the simultaneous determination of bepotastine and hydroxychloroquine concentrations in human breast milk and apply it in clinical practice. METHODS The milk samples （50 μL） were precipitated with 200 μL methanol containing the internal standard （100 ng/mL chloroquine）， and the supernatant was taken for analysis after vortexing and centrifugation. The separation was performed on a Waters ACQUITY UPLC HSS T3 column with mobile phase consisted of 0.1% formic acid-10 mmol/L ammonium acetate solution （phase A） and methanol （phase B） at gradient elution of 0.35 mL/min. The injection volume was 2 μL， and the analysis time was 4 min. The detection of the analytes was performed by electrospray ionization in positive mode by multiple reaction monitoring with the transition of m/z 388.9→201.9 （bepotastine）， m/z 336.3→247.1 （hydroxychloroquine）， and m/z 320.2→247.2 （chloroquine）. The established LC-MS/MS method was researched in methodology and used to determine the drug concentrations in the breast milk of 1 case of lactating patient. RESULTS The linear range of bepotastine was 2-200 ng/mL（ r＝0.999）， and hydroxychloroquine was 50-1 000 ng/mL （r＝0.998）. The intra-assay and inter-assay precisions were both ≤15%， and the accuracy， extraction recovery， matrix effect， and stability all met the acceptance criteria for bioanalytical method validation. The concentration result of bepotastine and hydroxychloroquine in the breast milk of the lactating patient showed， after 2 h and 14 h， the concentrations of bepotastine in the breast milk of the patient were 34.95 ng/mL and 5.72 ng/mL； those of hydroxychloroquine were 211.92 ng/mL and 104.18 ng/mL， respectively. The relative infant doses were 1.83% and 0.56%， respectively. CONCLUSIONS The established method is simple， rapid， and sensitive. It is suitable for simultaneous determination of bepotastine and hydroxychloroquine concentrations in human milk and can provide reference for safe drug use during lactation.

Simultaneous determination of bepotastine and hydroxychloroquine concentrations in human breast milk by LC-MS/MS / 中国药房

OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry （LC-MS/MS） method for the simultaneous determination of bepotastine and hydroxychloroquine concentrations in human breast milk and apply it in clinical practice. METHODS The milk samples （50 μL） were precipitated with 200 μL methanol containing the internal standard （100 ng/mL chloroquine）， and the supernatant was taken for analysis after vortexing and centrifugation. The separation was performed on a Waters ACQUITY UPLC HSS T3 column with mobile phase consisted of 0.1% formic acid-10 mmol/L ammonium acetate solution （phase A） and methanol （phase B） at gradient elution of 0.35 mL/min. The injection volume was 2 μL， and the analysis time was 4 min. The detection of the analytes was performed by electrospray ionization in positive mode by multiple reaction monitoring with the transition of m/z 388.9→201.9 （bepotastine）， m/z 336.3→247.1 （hydroxychloroquine）， and m/z 320.2→247.2 （chloroquine）. The established LC-MS/MS method was researched in methodology and used to determine the drug concentrations in the breast milk of 1 case of lactating patient. RESULTS The linear range of bepotastine was 2-200 ng/mL（ r＝0.999）， and hydroxychloroquine was 50-1 000 ng/mL （r＝0.998）. The intra-assay and inter-assay precisions were both ≤15%， and the accuracy， extraction recovery， matrix effect， and stability all met the acceptance criteria for bioanalytical method validation. The concentration result of bepotastine and hydroxychloroquine in the breast milk of the lactating patient showed， after 2 h and 14 h， the concentrations of bepotastine in the breast milk of the patient were 34.95 ng/mL and 5.72 ng/mL； those of hydroxychloroquine were 211.92 ng/mL and 104.18 ng/mL， respectively. The relative infant doses were 1.83% and 0.56%， respectively. CONCLUSIONS The established method is simple， rapid， and sensitive. It is suitable for simultaneous determination of bepotastine and hydroxychloroquine concentrations in human milk and can provide reference for safe drug use during lactation.

Clinical treatment and management of invasive fungal disease in recipients of solid organ transplantation / 器官移植

With widespread application of solid organ transplantation (SOT), the incidence of postoperative invasive fungal disease (IFD) in SOT recipients has been increased year by year. In recent years, the awareness of preventive antifungal therapy for SOT recipients has been gradually strengthened. However, the problem of fungal resistance has also emerged, leading to unsatisfactory efficacy of original standardized antifungal regimens. Drug-drug interaction and hepatorenal toxicity induced by drugs are also challenges facing clinicians. In this article, the characteristics of drug-drug interaction and hepatorenal toxicity among triazole, echinocandin and polyene antifungal drugs and immunosuppressants were reviewed, and postoperative preventive strategies for IFD in different types of SOT recipients and treatment strategies for IFD caused by infection of different pathogens were summarized, aiming to provide reference for physicians in organ transplantation and related disciplines.

Pharmacokinetics of rifampicin, isoniazid & pyrazinamide during daily & intermittent dosing: A preliminary study

Background & objectives: The National Tuberculosis (TB) Control Programme has transitioned from thrice-weekly to daily drug treatment regimens in India. This preliminary study was conceived to compare the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) in TB patients being treated with daily and thrice weekly anti-TB treatment (ATT). Methods: This prospective observational study was undertaken in 49 newly diagnosed adult TB patients receiving either daily ATT (n=22) or thrice-weekly ATT (n=27). Plasma RMP, INH and PZA were estimated by high-performance liquid chromatography. Results: The peak concentration (Cmax) of RMP was significantly higher (RMP: 8.5 ?g/ml vs. 5.5 ?g/ml; P=0.003) and Cmax of INH was significantly lower (INH: 4.8 ?g/ml vs. 10.9 ?g/ml; P<0.001) in case of daily dosing compared to thrice-weekly ATT. Cmax of drugs and doses was significantly correlated. A higher proportion of patients had subtherapeutic RMP Cmax (8.0 ?g/ml) during thrice-weekly compared to daily ATT (78% vs. 36%; P=0.004). Multiple linear regression analysis showed that Cmax of RMP was significantly influenced by the dosing rhythm, pulmonary TB and Cmax of INH and PZA by the mg/kg doses. Interpretation & conclusions: RMP concentrations were higher and INH concentrations were lower during daily ATT, suggesting that INH doses may need to be increased in case of a daily regimen. Larger studies are, however, required using higher INH doses when monitoring for adverse drug reactions and treatment outcomes.

Rapid determination of acetaminophen in plasma by LC-MS/MS / 中华劳动卫生职业病杂志

Objective: To establish a method for the rapid determination of acetaminophen (APAP) in human plasma by LC-MS/MS. Methods: The plasma samples were extracted by methanol and acetonitrile (1: 1) and purified directly. C(18) column was used for sample separation. The mobile phase were methanol (5 mmol/L ammonium acetate) and water (5 mmol/L ammonium acetate). Samples were analyzed by LC MS/MS with the electrospray ionization multi reaction monitoring (MRM) mode. Results: The calibration curves of APAP was linear in the concentration range of 0~10 mg/L, the correlation coefficient (r) was greater than 0.999 0. The relative standard deviation within and between batches was less than 10%. The recovery rate were 96.81%~101.7%. The detection limit of the method was 0.1 μg/L and the lower limit of quantification was 0.3 μg/L. Conclusion: This method has strong specificity, high sensitivity and reliable determination results. It is suitable for the rapid analysis of clinical plasma samples.

Method establishment and clinical practice for concentration determination of caffeine and its metabolites in urine / 中国药房

OBJECTIVE To establish a method for concentration determination of caffeine and its three metabolites， theophylline， paraxanthine and theobromine in urine， and apply it in clinical practice. METHODS Using caffeine-13C3-d3 as internal standard （IS）， and the urine samples were protein precipitated with acetonitrile； HPLC-MS/MS method was adopted to determine the concentrations of caffeine and its three metabolites. The determination was performed on Waters ACQUITY UPLC® BEH HILIC column with mobile phase consisting of 60 mmol/L ammonium acetate （A）-acetonitrile （B） （gradient elution） at the flow rate of 0.5 mL/min. The column temperature was set at 38 ℃ ， and the sample size was 2 μL. The electrospray ionization detection was operated in a positive mode by multiple reaction monitoring. The detection ions for quantitative analysis were m/z 195.1→110.0 for caffeine， m/z 181.1→124.0 for theophylline， m/z 181.1→124.0 for paraxanthine， m/z 181.1→138.0 for theobromine， and m/z 198.1→ 140.1 for IS. The above method was used to determine the concentrations of caffeine and its three metabolites in the urine of 19 infants with apnea of prematurity （AOP）. RESULTS The linear ranges of mass concentration of caffeine， theophylline， paraxanthin and theobromine were 0.200-200， 0.050-50.0，0.050 0-50.0， and 0.100-100 μg/mL， respectively. The lower limits of quantification were 0.200， 0.050， 0.050 and 0.100 μg/mL （r＞0.990）， respectively. RSDs of intra-day and intra- day precision were not above 10.37%， and matrix factors were 85.68%-109.90%； extraction recoveries were 93.53%-109.40% （RSD≤15%）， and RSDs of stability tests were all lower than 15%. The concentrations of caffeine and its three metabolites in the urine of 19 cases were （27.346±7.951）， （0.351±0.223）， （0.428±0.395） and （0.472±0.374） μg/mL， respectively. CONCLUSIONS The established HPLC-MS/MS method is simple， sensitive and can be used for the determination of caffeine and its three metabolites in urine samples of AOP.

Quantitative analysis of polymyxin B in human serum by LC-MS/MS / 药物流行病学杂志

Objective To develop a simple and sensitive LC-MS/MS method for the determination of polymyxin B in human serum.Methods Polymyxin E2 was used as an internal standard and acetonitrile(0.1%formic acid)was used for protein precipitation.Chromatographic separation was performed on a Hypersil GOLDTM C18 column.Mobile phase A was 0.1%formic acid in water,and mobile phase B was methanol.The flow rate was 0.4 mL·min-1,with gradient elution.The column temperature was 40℃.The injection volume was 2 μL and the analysis time was 3.3 min.Multiple reaction monitoring and electrospray ion source positive ion mode were applied for quantitative analysis.The quantitative analysis ion pairs were m/z 402.10>101.10(polymyxin B1),m/z 397.45>101.10(polymyxin B2),m/z 578.50>101.10(polymyxin E2).Results The linear relationship of polymyxin B1 was at 22-15 000 ng·mL-1 and B2 was at 5-1 700 ng·mL-1 in human serum,which achieved excellent linearity,and the correlation coefficient was higher than 0.999 0.The lower limit of quantification of polymyxin B1 and B2 were 22 ng·mL-1 and 5 ng·mL-1,respectively.The accuracies were 95.98%-104.60%for polymyxin B1,98.11%-105.59%for polymyxin B2,respectively.The RSDs of intra-and inter-day precision were less than 15%.The recoveries of polymyxin B1 and B2 were 97.26%-103.31%and 95.81%-101.22%,respectively,and the matrix effects were 96.52%-109.54%and 93.29%-109.95%,respectively.The RSDs of the samples were all less than 15%.The mean AUC0-24h was(72.85±17.87)mg·h·L-1 in six patients.Conclusion The established LC-MS/MS method for determining polymyxin B in human serum meets the requirements of biological sample analysis.It is suitable for determining polymyxin B in human serum.

Changes of anesthetic drug concentration in plasma during isolation of autologous blood with acute isovolumic hemodilution and its influence on anesthetic effect after reinfusion / 中国临床药理学与治疗学

To investigate the changes of anesthetic drug concentration in plasma during isolation of autologous blood with acute normovolemic hemodiluti-on and its influence on the depth of anesthesia, muscle relaxant effect and blood drug concentration after reinfusion. METHODS: Forty patients of both sexes, aged 20-60 yr, American Society of Anesthesiologists physical status or Ⅱ, hemoglobin (Hb) >120 g / L, hematocrit (Hct) >35%, undergoing eletive multilevel spinal surgery were included, were divided into 2 groups (n=20 each) using a random number table. ANH group (group A): ANH was performed after stable induction of anesthesia, the target Hct value was 28%-30%, and autologous blood was reinfused after the main operation steps. Control group (group C): routine transfusion and infusion treatment. The bispectral index (BIS) and Train-of-Four stimulation (TOF) were observed and recorded at the stable induction of anesthesia (T1), 30 minutes of stable induction (T2), the end of operation (T3), 30 minutes after the end of the operation (T4), 1 hour after the end of the operation (T5) and 2 hours after the end of the operation (T6). The concentrations of propofol and cisatracurium besylate in plasma at T1-T6, stored blood at 1 h (TS1), 2 h (TS2), and before reinfusion (TS3) were detected by Liquid Chromatography-tandem Mass Spectrometry. The extubation time and recovery score at T4-6 hours were recorded. RESULTS: There was no significant difference in propofol between the two groups at each time point (P > 0.05). The plasma concentration of cisatracurium besylate in group A was higher than that in group C at T3 (P0.05). The BIS value at T4 and TOF value at T3 in group A were significantly lower than those in group C. The recovery score of group A was lower than that of group C at T4 (P0.05). CONCLUSION: The plasma concentrations of propofol and cisatracurium besylate were basically unchanged during the in vitro isolation of ANH autologous blood. The plasma concentrations of cisatracurium besylate were only temporarily affected after the main operation steps, but the postoperative muscle relaxation recovery and recovery quality were not significantly affected.

Analysis of individualized diagnosis and treatment of urosepsis patient / 中国中西医结合急救杂志

Objective Combined with domestic and foreign guidelines,to explore the individualized treatment strategy of urosepsis,and to provide reference for standardized diagnosis and treatment of urosepsis patient.Methods To analyze the diagnosis and treatment process of a patient with urogenic sepsis who was admitted to the department of critical care medicine of the First Affiliated Hospital of Xi'an Jiaotong University in April 15,2021.During the diagnosis and treatment process,we performed puncture drainage fluid and urine culture as soon as possible to confirm the diagnosis from the perspective of etiology.Considering the possible pathogenic bacteria at the infection site,the drug resistance of pathogenic bacteria in medical units,and drug safety,imipenem and cilastatin was chosen for anti-infective therapy.A two-step approach was used for drug administration based on drug pharmacokinetics/pharmacodynamic(PK/PD)characteristics,and drug concentration monitoring.The patients were followed up after discharge.Results The patient was critically ill on admission and was diagnosed with urosepsis.We optimize the empirical use of antimicrobials based on their PK/PD characteristics.Ultrasound-guided percutaneous nephrostomy of the left renal pelvis was performed to adequately drain the infection.Urine culture returned as extended-spectrum β-lactamase(ESBL)-producing Escherichia coli,confirming the etiological diagnosis.After 7 days of treatment,the patient's condition improved,the antibacterial drugs were downgraded to piperacillin-tazobactam,and the total course of anti-infection was 14 days.The patient was in good condition 2 months after discharge,and underwent left ureteral calculus and lithotripsy in the local hospital,and the left nephrostomy tube was removed.After discharge,the patient's condition was stable,no recurrence was found after 7 months of follow-up,and daily life was not affected.Conclusions Management of infection foci in urosepsis patient is critical.Diagnosis and treatment should refer to domestic and foreign guidelines,and formulate treatment strategies based on the distribution of local pathogens,drug resistance,and the actual clinical conditions of patients.Optimize the use of antibiotics based on drug PK/PD characteristics,monitor the concentration of therapeutic drugs,and realize individualized treatment.

Study on the relationship between blood concentration and efficacy of voriconazole in the treatment of pediatric invasive fungal infection / 药学实践杂志

Objective To explore the correlation between dose, blood concentration and efficacy of voriconazole in the treatment of invasive fungal infection in children. Methods 68 children treated with voriconazole during January 2019 to December 2019 were collected. The plasma concentration of voriconazole was assayed by high performance liquid chromatography (HPLC). The correlation between blood concentration and clinical efficacy was statistically analyzed. Results Different drug blood concentrations were obtained with different dosages: <4.0 mg/kg (6 cases) with the trough concentration ranged from 0.4 to 3.31 μg/ml (r=0.613, P=0.195). (4.0 - 7.0) mg/kg (44 cases), ranged from 0.35 to 7.02 μg/ml (r=0.325, P=0.018); >7.0 mg/kg (18 cases), ranged from 1.46 to 12.45 μg/ml (r=0.584，P＜0.023). There was a difference between the three groups (F=7.270, P=0.026). The relationship between the drug blood concentration and the therapeutic effect was obvious. In the <1.0 μg/ml group of 14 cases, 10 cases (71.4%) were effective, and 4 cases were ineffective. In the 1.0 - 5.5 μg/ml group of 48 cases, 44 cases (91.7%) were effective, and 4 cases were ineffective. In the >5.5 μg/ml group of 6 cases, 4 cases (66.7%) were effective and 2 cases ineffective. The difference among the three groups was obvious (χ2=5.360, P=0.039). Among the 68 cases, 58 cases (85.3%) were effective, and 10 cases (14.7%) were ineffective. Adverse reactions occurred in 10 cases (14.7%) with mild liver function injury, which did not affect the treatment and recovered with liver protection treatment. Conclusion This study showed that voriconazole was generally safe and effective in the treatment of invasive fungal infections in children. There was a significant dose-blood concentration and efficacy correlation. Further studies on pharmacokinetics and efficacy should be carried out to optimize the individualized treatment.

Effects of altitude hypoxia on cerebral blood distribution of sodium valproate in mice / 中国药理学通报

Aim To investigate the effects of altitude hypoxia on serum sodium valproate eoncentration and eerebral blood distribution.Methods Male mice were divided into control group and plateau group.Each group was given sodium valproate orally and intrave¬nously, respectively.UFLC-MS/MS was used to deter¬mine the concentration of sodium valproate in plasma and brain, and Western blot was used to detect the ex¬pression of P-gp in BBB.Results Compared with the control group, the ratio of brain/blood drug concentra¬tion in plateau group was up-regulated by 44.0% , 57.9% , 176.8% and 184.5% at 10, 30, 60 and 120 min, respectively.The ratio of brain/blood drug con-centration increased by 33.9% , 50.6% and 125.6% at 60 min, 120 min and 240 min in plateau group, re¬spectively.Compared with the control group, the ex¬pression of P-gp protein in BBB of mice in altitude group was significantly down-regulated by 58.46% (P < 0.05 ).Conclusions Compared with the control group, the brain/blood drug concentration ratio of val¬proic acid increases in high altitude hypoxia environ¬ment.Meanwhile, it is found that P-gp expression lev-el decreased in the brain mierovessels of mice under high altitude hypoxia environment, and the cerebral and blood distribution of valproic acid in mic increases in high altitude hypoxia environment.

Determination of prucalopride in human plasma by LC-MS/MS analysis / 中国药理学通报

Aim To develop an LC-MS/MS method for the determination of prucalopride(PCP)in human plasma.Methods Prucalopride -13CD3(dPCP)was used as the internal standard.The analytes were extracted from human plasma through liquid-liquid extraction method using ethyl acetate, followed by being dried, and then the reconstitution was injected into LC-MS/MS systems.Agilent ZORBAX SB C18(3.0×100 mm, 3.5 μm)column and isocratic elution system composing of methanol and 1 mmol·L-1 ammonium acetate(80:20, V/V)provided chromatographic separation of PCP and dPCP.AB Sciex API4000 mass spectrometer equipped with an electrospray ionization source in positive ion mode was employed for mass detection, and data acquisition was carried out in multiple reaction monitoring(MRM)mode.The mass transition ion-pair was followed as m/z 368.4/196.0 for PCP and m/z 374.4/198.0 for dPCP.Results PCP and dPCP were eluted at 3.6 min, with no interference in human blank plasma.PCP in human plasma showed good linearity over the concentration range of 0.058 96-7.547 μg·L-1 with the correlation coefficient of 0.996 3-0.999 6.The lower limit of quantitation of this method was 0.058 96 μg·L-1.The intra-batch and inter-batch accuracy ranged from 98.29% to 108.2%, with good precision(CV<5.2%).The average matrix factors of normal, haemolysed and lipaemic matrix human samples all ranged from 96.48% to 106.3% with CV less than 8.39%.The average extraction recoveries of PCP at low, medium and high concentrations were 89.88%, 95.27% and 94.52% respectively, with CV less than 7.21%.PCP was stable in human samples after 6 h at room temperature, 60 h at -20 ℃, 56 days or three freeze-thaw cycles at -80 ℃; meanwhile, the processed plasma samples remained stable after being stored for 24 hours in autosampler at 8 ℃.Furthermore, PCP in human blood samples was proved to be stable after 4 h at room temperature.Conclusions The present LC-MS/MS method for the determination of PCP in human plasma was convenient, accurate, sensitive, stable, specific and reproducible and was proved to be suitable for the clinical pharmacokinetics and bioequivalence studies of PCP preparations.

Establishment of ultra performance liquid chromatography-tandem mass spectrometry method for measuring plasma caffeine concentration / 中华检验医学杂志

Objective:To establish an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for plasma caffeine concentration detection, and to explore the clinical value of caffeine therapeutic drug monitoring (TDM) in the treatment of premature infants with respiratory distress syndrome (RDS).Method:Take the plasma sample in a centrifuge tube, add the caffeine deuterated isotope internal standard, then add the protein precipitant, vortex the mixture thoroughly, and centrifuge the supernatant to enter the mass spectrometry analysis. The mobile phase were methanol and water, gradient elution; the column temperature was 45 ℃, the method was established using Shimadzu LC-30AD-CL liquid system and AB SCIEX 4500 QTRAP mass spectrometer, and the sensitivity, specificity, linearity, accuracy imprecision, matrix effect, and carry-over of the method were evaluated. Sample from 30 patients diagnosed with neonatal RSD were collected in the Department of Neonatology of Renmin Hospital of Wuhan University from February to April 2021, then detected the trough concentration of caffeine in premature infants with RDS after taking the same dose of caffeine to assess the impact of individual variation on caffeine drug concentration.Results:The detection limit of caffeine was 0.02 μg/ml, and the lowest limit of quantification was 0.05 μg/ml. It showed good linearity ( R2=0.9986, R>0.99) in the concentration range from 1.0 to 100.0 μg/ml, specificity (recovery rate of 85.52%-114.12%), accuracy (recovery rate 85.97%-114.53%), intra-day and inter-day imprecision ( CV 6.01%-11.28%), matrix effects and carryover pollution were negligible. The trough concentration of 30 preterm infants with RSD after taking the same dose of caffeine (10 mg/kg) was (25.45±11.61) μg/ml, and the coefficient of variation was 44.88%. Conclusion:This study established an accurate and reliable UPLC-MS/MS method with low sample consumption to monitor the blood concentration of caffeine; caffeine TDM has certain clinical application value, which can be used to assist RDS diagnosis and treatment and improve the efficacy of caffeine.

Effect of acute normovolemic hemodilution autologous blood transfusion on the EEG bispectral index and muscle relaxation in elderly patients undergoing orthopedic surgery / 中国临床药理学与治疗学

AIM: To observe the effect of acute normovolemic hemodilution (ANH) autologous blood transfusion on the EEG bispectral index and muscle relaxation in elderly patients undergoing orthopedic surgery to explore the influence of autologous blood transfusion containing anesthetic components on the quality and safety of postoperative anesthesia recovery. METHODS: Forty patients, aged 65-75, weighing 55-80 kg, ASA grade I-II, with an estimated intraoperative blood loss of more than 600 mL, were selected for elective orthopedic surgery. The patients were randomly divided into two groups (n=20): group A was given acute normovolemic hemodilution (ANH), and the target value of Hct was 28%-30% after induction of anesthesia; group B was the control group which was given routine fluid infusion during operation without ANH. Bispectral index (BIS), TOF values and plasma concentrations of propofol and cisatracurium were measured at the beginning of autotransfusion (T

Analysis of clinical pharmacists participating in the treatment of a case of sodium valproate poisoning / 药学实践杂志

Objective To explore the role of clinical pharmacists in the treatment of drug poisoning by analyzing the clinical pharmacist's participation in the treatment of a patient with sodium valproate poisoning. Methods Clinical pharmacists measured the plasma concentration of sodium valproate to inform the doctor to diagnose illnesses. At the initial stage when the concentration is high, to eliminate the free drug by continuous venous-venous hemodialysis-filtration (CVVHDF). Then, the combined drug was cleared by hemoperfusion (HP). Results The blood concentration dropped by half at the first CVVHDF and decreased obviously after two HPs. After stable observation in five days’ course of disease, the blood concentration was maintained at a low level and the patient was cured and discharged. Conclusion The implementation of the blood purification program under the monitoring of the blood drug concentration with the participation of pharmacists is helpful for the rescue of drug overdose and is worthy of promotion.

Research progress on the gene polymorphism of tacrolimus transporter in organ transplantation / 器官移植

Tacrolimus (Tac) is a commonly used immunosuppressant after organ transplantation, which has high immunosuppressive efficacy. However, the pharmacokinetics of Tac significantly differ among individuals, and gene polymorphism is the main influencing factor. In recent years, the gene polymorphism of drug transporter has become a novel research hotspot. Nevertheless, the effect of the gene polymorphism of transporter on Tac pharmacokinetics remains controversial. Consequently, the correlation between the gene polymorphism of transporter and Tac blood concentration plays a significant role in guiding Tac-based individualized immunosuppressive therapy. In this article, the research progresses on the gene polymorphism of adenosine triphosphate-binding cassette (ABC) transporter and solute carrier (SLC) transporter in organ transplantation was reviewed. The correlation between the gene polymorphism of transporter and Tac blood concentration was summarized, aiming to provide reference for Tac-based individualized therapy.

Simultaneous determination of rosuvastatin, atorvastatin and their metabolites in human plasma by UPLC-MS/MS / 国际药学研究杂志

Objective: To develop a ultra performance liquid chromatography- tandem mass spectrometry(UPLC- MS/MS) method for the simultaneous determination of rosuvastatin(RT), atorvastatin(AT)and their metabolites, i.e., atorvastatin lactone (ATL), ortho- hydroxy-atorvastatin(O-AT)and para-hydroxy-atorvastatin(P-AT), in human plasma. Methods: Deuterium-labeled compounds, RT-d6, AT-d5 and P-AT-d5 were used as the internal standards(IS). The plasma samples were extracted with ethyl acetate. The chromatographic separation was achieved on a ACQUITY UPLCTM BEH C18 column(50 mm×2.1 mm, 1.7 μm)with the mobile phase of 0.2%(v/v)formic acid aqueous solution and methanol by gradient elution. The flow rate was 0.2 ml/min, and the column temperature was 40℃. Analytes were detected on a tandem mass spectrometer, equipped with an electrospray ionization source that was operated in the positive mode. The selectivity, standard curve, precision and accuracy, extraction recoveries, matrix effect, and stability were investigated. Results: The linear range of RT was 0.1-50 ng/ml with r2 =0.9977. The linear range for AT, ATL, O-AT and P-AT was 0.05-50 ng/ml with r2 =0.9997, 0.9988, 0.9923 and 0.9995, respectively. Conclusion: The established method is rapid, sensitive, accurate, specific and reliable, which is suitable for the simultaneous determination of RT, AT and their metabolites in human plasma.

Comparison between daptomycin plasma concentration in left ventricle and that in right ventricle of rats / 中国中西医结合急救杂志

Objective To detect the plasma concentrations of daptomycin in the left ventricle and right ventricle of rats by high-performance liquid chromatography-mass spectrometry(LC-MS/MS), and evaluate the therapeutic effect of daptomycin on left ventricular endocarditis. Methods Thirty-five healthy Sprague-Dawley (SD) rats were divided into a normal saline group (5 rats) and a daptomycin group (30 rats) according to the random number table method. The daptomycin group was subdivided into 6 subgroups according to the times of blood collection (0.25, 0.5, 1, 2, 4, 8 hours), with 5 rats in each subgroup. The normal saline group was given 4 mL/kg normal saline; the daptomycin group was injected with 50 mg/kg daptomycin into the tail vein. The blood samples from left ventricle and right ventricle were extracted at the corresponding time points, the plasma concentrations of daptomycin group were determined by high performance liquid chromatography-mass spectrometry (HPLC-MS) and the differences of left ventricular and right ventricular plasma concentrations were compared at different time points. The plasma in normal saline group was the blank plasma that was used for HPLC-MS methodological evaluation. Results There were no statistical significant differences between the left ventricle and right ventricle in plasma concentrations of daptomycin at 0.25, 0.5, 1, 2, 4, and 8 hours after administration (g/L: 2.67±0.30 vs. 2.77±0.31, 1.77±1.27 vs. 1.64±0.55, 1.35±0.40 vs. 1.36±0.41, 0.97±0.07 vs. 0.92±0.09, 0.73±0.16 vs. 0.65±0.18, 0.07±0.06 vs. 0.06±0.05, respectively all P > 0.05). Conclusion There are no significant differences between the left ventricle and right ventricle in plasma concentrations of daptomycin. It is speculated that daptomycin may have the same therapeutic effect on left endocarditis.

Therapeutic monitoring of cerebrospinal fluid vancomycin concentrations and analysis of their influencing factors in neurosurgical intensive care unit patients / 中华危重病急救医学

Objective To evaluate cerebrospinal fluid (CSF) vancomycin concentrations and identify factors influencing CSF vancomycin concentrations in critically ill neurosurgical patients. Methods A retrospective study was conducted. Adult patients who received vancomycin treatment and CSF vancomycin concentrations monitoring admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from January 2016 to June 2019 were enrolled. General information, vancomycin dosing regimens, CSF vancomycin concentrations, CSF drainage methods and volume of the previous day, and concurrent medications, etc. were collected for analysis. CSF vancomycin concentrations of patients with definite or indefinite central nervous system (CNS) infection, different vancomycin dosing regimens and their influencing factors were analyzed. Results A total of 22 patients were included. 168 CSF specimens were collected for culture, 20 specimens of which were culture positive, with a positive rate of 11.9%. Sixty cases of CSF vancomycin concentration were obtained. Among the 22 patients, 7 patients (31.8%) were diagnosed with proven CNS infection, 11 patients (50.0%) clinically diagnosed, 2 patients (9.1%) diagnosed with uncertain CNS infection, and 2 patients (9.1%) diagnosed without CNS infection. Intravenous (IV) administration of vancomycin alone was used in 15 cases (25.0%), intrathecal injection in 17 cases (28.3%), IV+intrathecal injection in 23 cases (38.3%), and IV+intraventricular administration in 5 cases (8.3%). The CSF vancomycin concentrations ranged from < 0.24 to > 100 mg/L, with an average level of 14.40 (4.79, 42.34) mg/L.①Administration methods of vancomycin affected CSF vancomycin concentrations. The CSF vancomycin concentration with intrathecal injection or intraventricular administration was higher than that of IV administration alone [mg/L: 25.91 (11.28, 58.17) vs. 2.71 (0.54, 5.33), U = 42.000, P < 0.01].②When vancomycin was administered by IV treatment alone, CSF vancomycin concentrations were low in both groups with definite CNS infection (proven+probable) and indefinite CNS infection (possible+non-infection), the CSF vancomycin concentrations of which were 4.14 (1.40, 6.36) mg/L and 1.27 (0.24, 3.33) mg/L respectively, with no significant difference (U = 11.000, P = 0.086).③CSF vancomycin concentrations rose with the increased dose of vancomycin delivered by intrathecal injection or intraventricular administration. According to the dose of vancomycin administered locally on the day before therapeutic drug monitoring (TDM), cases were divided into the following groups:0-15 mg group (n = 22), 20-35 mg group (n = 33), and 40-50 mg group (n = 5), the CSF vancomycin concentrations of which were 4.14 (1.09, 8.45), 30.52 (14.31, 59.61) and 59.43 (25.51, 92.45) mg/L respectively, with significant difference (H = 33.399, P < 0.01). Moreover, the cases of CSF vancomycin concentration of≥10 mg/L accounted for 18.2%, 84.8% and 100% of these three groups, respectively. CSF vancomycin concentrations mostly reached target level when dose of vancomycin administered locally were 20 mg/L or more. Conclusions It is difficult to reach target CSF vancomycin concentration for critically ill neurosurgical patients with or without CNS infection by IV treatment. Local administration is an effective treatment regimen to increase CSF vancomycin concentration.