Objective To evaluate the protective effect of Pedicularis rex (P.Rex) on liver fibrosis in mice. Methods Kunming mice were randomly divided into groups (n=10) of normal control group, model control group, colchicine (0.1 mg·kg-1) group, low (200 mg·kg-1), medium (400 mg·kg-1) and high (800 mg·kg-1) doses of P.rex;The liver fibrosis model was established by intraperitoneal injection of CCl4 (1 mL·kg-1).At the beginning of the 5th week, drugs were given intragastrically once a day for seven consecutive weeks.One hour after the last administration, all mice were anesthetized and the whole blood samples were collected for the determination of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), laminin (LN), procollagen type Ⅲ (PC Ⅲ), and collagen type Ⅳ (Ⅳ-C) levels;organs were then taken out and weighed for the calculation of mouse organ coefficients;liver tissues were tested by Western blotting for TGF-b1, Smad3, α-SMA, and Collagen I proteins;HE and Masson staining were used for pathological morphology examination of mouse liver tissue. Results The fur of mice in the model control group was erected, and the mice have reduced activity and slow response.The general status of the mice in the P.rex groups was better than that in the model control group.Compared with those levels in the model group, the serum ALT, AST, HA, LN, PCⅢ, and Ⅳ-C levels of mice in all P.rex groups were decreased significantly (P<0.01).All doses of P.rex reduced the degree of liver fibrosis induced by CCl4 and significantly down-regulated the expressions of TGF-β1, Smad3, α-SMA, and collagen I proteins (P<0.01). Conclusion P.rex had a good protective effect on CCl4-induced liver fibrosis in mice, and the effect might be related to its inhibition in TGF-β1/Smad signaling pathway and down-regulation of the α-SMA and collagen I protein expression.
Objective To establish a LC-MS/MS method for the simultaneous determination of oridonin and ponicidin in rat plasma, and to study the pharmacokinetic characteristics of oridonin and ponicidin at different doses of donglingcao dropping pills. Methods Different doses of donglingcao dropping pills were administrated at low (0.3 g·kg-1), medium (0.9 g·kg-1), high (2.7 g·kg-1), and cumulative dosage (25 mg·kg-1, 7days), respectively.Diphenhydramine was chosen as the internal standard, and LC-MS/MS was used to determine the concentrations of oridonin and ponicidin in rat plasma.Then concentration-time curves were obtained.Pharmacokinetic parameters were calculated by DAS 3.0 software. Results After the administration of the pills at low, medium and high doses, the peak concentrations (Cmax) of oronidin at doses of 0.3, 0.9, and 2.7 g·kg-1 were (74.25±29.93), (197.67±38.09), and (346.03±34.87) ng·mL-1, respectively.The AUC0-ts were (85.46±36.06), (187.21±44.27), and (654.66±88.50) ng·mL-1·h, respectively.The Cmaxs of ponicidin at doses of 0.3, 0.9, and 2.7 g·kg-1 were (30.33±16.15), (37.88±11.95), and (60.92±36.60) ng·mL-1, respectively.The AUC0-ts were (17.44±4.16), (70.77±33.31), and (136.25±3.65) ng·mL-1·h, respectively.The elimination half-life (t1/2β) of oronidin at single dose and multiple doses of 0.9 g·kg-1 were (2.24±1.17) and (2.85±0.82) h, respectively.The t1/2β of ponicidin at a single dose and multiple doses of 0.9 g·kg-1 were (2.56±0.45) h and (2.73±0.62) h, respectively. Conclusion After low (0.3 g·kg-1), medium (0.9 g·kg-1), and high ( 2.7 g·kg-1) doses of donglingcao dropping pills were administrated, the AUC0-t of oridonin showed linear dynamic characteristics, and there was no accumulation in the body at the medium dose of single and multiple doses administration.
Tacrolimus, as a new immunosuppressant, has been widely used in the prognosis of various organ transplantation with remarkable therapeutic effect.In the long-term clinical use, it was found that tacrolimus had a strong individual metabolic differences and narrow therapeutic window, which made it difficult to give a reasonable administraion dose, resulting in postoperative transplantation dysfunction and multiple adverse reactions, thus seriously reducing the survival rate of transplanted organs.Studies have shown that metabolic enzymes are important genetic factors affecting tacrolimus metabolism.In addition, transporters are also closely related to tacrolimus metabolism.The study of gene polymorphism of transporters is of great significance for the efficacy of tacrolimus.This paper reviews the main uptake or efflux transporters of tacrolimus, mainly including the effects of P-gp, MRP, OATP, ZnT8 and CNT3 on the efficacy and adverse reactions of tacrolimus.Some research conclusions can guide clinical medication and provide basis for the personalized treatment of organ transplantation patients.
Objective To establish individualized drug therapy strategy for hemophagocytic syndrome (HPS) patients after liver transplantation. Methods By participating in the diagnosis and treatment of a patient with HPS after liver transplantation, clinical pharmacists collaborated with doctors to integrate therapeutic drug monitoring, pharmacokinetic characteristics and plasma exchange drug clearance characteristics with effective etiological and supportive treatment, including establishing immunosuppressive and immunomodulatory strategies, adjusting anti-infective regimen, using blood products and adopting blood purification method. Results The patient was generally discharged from the hospital after a good recovering, and has been followed up for more than 1 year and a half, and has survived healthily. Conclusion It is highly suggested that clinical pharmacists actively involved in treatment of rare, difficult, and severe disease to evaluate the efficacy and tolerability of concomitant medication and design the individualized dosing regimens.It will largely contribute in the improvement of pharmaceutical care and promote the safety and effectiveness of drug use in patients after liver transplantation.
Objective To systematically evaluate the relationship between drug gene polymorphism and dose-normalized sirolimus (SRL) blood concentration (C/D) in renal transplant patients, so as to provide an evidence-based reference for clinical individualized application of SRL. Methods PubMed, Embase, Cochrane Library, CBM, and other database were searched online from the date of the database establishment to September 2021 to collect relevant studies.Rev Man 5.4.1 software was used to perform meta-analysis after selected literatures. Results A total of 10 related studies (2 in Chinese and 8 in English) were included, including 750 patients.There were 8 studies involving CYP3A5*3 and 7 studies involving MDR1 C3435T.The results of Meta-analysis showed that the difference of SRL C/D between CYP3A5*1 carriers and CYP3A5*3/*3 carriers was statistically significant [MD=-45.29,95%CI (-59.39, -31.20), P<0.000 01].For MDR1 C3435T gene, the results of each genetic model showed that there was no significant difference.There were only two studies involving CYP3A4*1B, and the studies conclusions were opposite;There was only one study involving CYP3A4*18B, and there was no correlation between CYP3A4*18 gene polymorphism and SRL C/D;There was only one study involving CYP3A4 rs2242480.The study showed that the gene polymorphism was related to the valley concentration of SRL after taking SRL for 1 year;There are 3 studies involving MDR1 C1236T and MDR1 G2677T/A. Conclusion At present, the study of the effect of drug gene polymorphism on SRL blood concentration in renal transplant recipients involves CYP3A4*1B, CYP3A4*18, CYP3A4*22, CYP3A4 rs2242480, CYP3A5*3, MDR1 C3435T, MDR1 C1236T, and MDR1 G2677T/A.The main researched genes are CYP3A5*3 and MDR1 C3435T.CYP3A5*1 carriers need to increase the SRL dose to reach the required concentration range.Analyzing the receptor CYP3A5*3 gene polymorphism can provide a reliable reference index for the individualized medication of SRL after the renal transplantation.MDR1 C3435T, C1236T, and G2677T/A gene polymorphisms have no correlation with SRL C/D, so routine detection is not recommended.The correlation between CYP3A4 gene polymorphism and SRL C/D needs to be further studied.
Cytomegalovirus (CMV) is the most common source of infection after organ transplantation.In addition to infection, CMV increases the risk of organ transplant complications, leading to higher rates of transplantation failure and mortality.Prevention and treatment of CMV infection are critical to the outcome of transplantation.Several new antiviral agents have recently emerged, including letermovir, maribavir, and brincidofovir, offering new treatment options for transplant patients against CMV infection.
The management of immunosuppressive therapy after renal transplantation is the key to improve the survival rate of patients and transplanted kidneys.However, immunosuppressive therapy is a double-edged sword.Insufficient immunosuppressive therapy will increase the risk of rejection, while excessive immunosuppressive therapy may lead to the impaired immune function.Due to the influence of long-term immunosuppressive therapy after transplatation, it is more common for transplant recipients to develop immune dysfunction.At present, there is no optimal immunosuppressive therapy recommended for patients with low immune function, and how to select immunosuppressive agents is still controversial.This review deeply analyzes the impact of immunosuppressive agents commonly used in renal transplantation on immune function, especially on clinical related immune detection indicators, and explore immune induction and immune maintenance strategies for different types and degrees of immune dysfunction in combination with the evaluation of the overall immune status of renal transplant recipients.It could provide references for precise immunosuppressive therapy for adult renal transplantation with low immune function.
Objective To explore the medical treatment strategy and pharmaceutical care of early lesions of posttransplant lymphoproliferative disease (PTLD) after pediatric liver transplantation. Methods The drug treatment process of 5 children with Epstein Barr virus (EBV) related PTLD after liver transplantation in Beijing Friendship Hospital Affiliated to the Capital Medical University from 2015 to 2019 was analyzed retrospectively, and the key points of pharmaceutical care were also analyzed. Results After the diagnosis of PTLD, the children were reduced the dose or stopped the use of immunosuppressant, and were treated with one or two cycles of rituximab.The latest follow-up time of 5 children was 17-24 months after treatment.Currently, the transplanted liver function was stable, and PTLD was relieved, and EBV viral load remained negative persistently. Conclusion PTLD is a serious complication after liver transplantation.There was no unified consensus on the treatment of PTLD.Reducing or stopping immunosuppressive agents and using rituximab can achieve a satisfactory efficacy for EBV-related PTLD patients after pediatric liver transplantation.Strengthening pharmaceutical care can ensure the safety and effectiveness of medication for children.
Objective Summarize the pharmaceutical care of a child with lung transplantation after stem cell transplantation, and accumulate experience in the treatment and pharmaceutical care of related diseases. Methods Clinical pharmacist participated in the treatment of a 6-year-old child after lung transplantation.According to the domestic and foreign literature and the pharmacological characteristics of the drug combined with the results of therapeutic drug monitoring (TDM), adjust and optimize the dosing regimen to monitor adverse drug reactions. Results The clinical pharmacist assisted the physician in optimizing the treatment plan of the child, so that the child survived for 62 days. Conclusion Children's special PK/PD and drug selection were quite different from adults.The formulation of drug plan needs to make individualized drug administration plan by means of therapeutic drugs, monitoring pharmacy and other means combined with patient's test indexes, carry out pharmaceutical monitoring on patients after lung transplantation, and cooperate with physician and nurses to improve the safety and effectiveness of patients' medication.
Objective To assess the clinical efficacy and safety of tacrolimus(TAC)combined with glucocorticoid(GC)in the treatment of Vogt-Koyanagi Harada(VKH)syndrome. Methods The clinical data of 17 VKH patients(33 eyes)who were first diagnosed in Tongji Hospital,Tongji Medicine College,Huazhong University of Science and Technology from January 2019 to April 2021 were retrospectively analyzed.There were 8 females and 9 males,and among them,one case had 1 eye,and the rest had both eyes.The average age was(42.65±3.83)years old.All the patients were treated with oral TAC combined with intravenous GC after the admission.The initial dose of the GC was 1.5-2.5 mg·kg-1·d-1,then was gradually reduced to 40-60 mg·d-1.After switching to oral administration,the dose was gradually reduced until stopped,and the total duration of GC was moderately shortened.The initial dose of TAC was 2 mg·d-1,and the blood concentration was regularly monitored.The dosage was adjusted to maintain the valley blood concentration of TAC at 5-10 ng·mL-1 and the follow-up time was at least 6 months.Main outcome indicators were visual acuity,inflammation of the anterior and posterior segments,GC use time,and the degree of retinal edema or detachment in the macular area as shown by the optical coherence tomography (OCT). Results Compared with the pre-treatment,the visual acuity in affected eyes were significantly improved after 6 months of treatment using TAC combined with GC (0.22±0.08 vs. 1.06±0.03,P<0.01);After 3 months of combination treatment,the proportions of eyes with corneal (keratic precipitates,KP),anterior chamber flash,optic disc hyperemia and edema,and retinal edema/exudative detachment were decreased (9.09% vs. 48.88%,15.15% vs. 69.7%,0.00% vs. 51.2%,3.33% vs. 78.79%,P<0.01);After 6 months of combination treatment,the proportions of eyes with extensive or multiple focal detachment of the retinal neuroepithelial layer and partial neuroepithelial detachment in the macular area were significantly reduced (0.00% vs. 66.67%,9.09% vs. 33.33%,P<0.01).During the treatment period,the liver and kidney function indexes of all patients were no statistically different with those before treatment. Conclusion The therapy of TAC combined with GC for VKH patients who were first diagnosed is an effective and safe option,and can be used as the first-line therapy for VKH.
Dexmedetomidine is a non-benzodiazepine sedative with multiple good properties of sedative, anti-inflammatory, anti-stress,and hemodynamic stability effects, and has a slight degree of inhibitory effect on respiratory system.Butorphanol, a new type of opioid, has mild adverse effects such as respiratory depression, gastrointestinal discomfort, and physical dependence.Dexmedetomidine combined with butorphanol can provide more effective sedation and analgesic effects, and has superiorities of opioid-sparing effect, maintaining hemodynamic stability, and reducing adverse effects of respiratory depression, nausea and vomiting, hypotension, bradycardia and delirium.The combination is currently used in clinical practice such as clinical anesthesia, postoperative analgesia, sedation and analgesia in the intensive care unit, and as a comfort medicine.
Hypoxia is a state of insufficient oxygen supply in cells or organisms.It can occur in the microcirculation damage or hypoperfusion of various tissues and organs.In normal adults, renal blood flow accounts for 20 to 25 percent of cardiac output in a normal calm state, so slight changes in hemodynamics can easily lead to renal hypoxia.Hypoxia-inducible factor (HIF) is a transcription factor that helps cells sense and adapts to changes in oxygen.Adaptation of cells and tissues to hypoxia stress under hypoxia conditions results in HIF activating a series of genes transcription.These genes are involved in angiogenesis, iron metabolism, glucose metabolism, and cell proliferation and apoptosis.Recent evidence suggests that HIF and hypoxia response play an important role in the development of various acute kidney injury (AKI) and chronic kidney disease (CKD).This article will discuss the regulatory mechanism of HIF, the role of related target genes in renal disease, and therapeutic prospects of related drugs in renal disease.
Objective To analyze the solubility and permeability of carbamazepine active pharmaceutical ingredient (API), and to compare the intrinsic dissolution rate of APIs from different sources, and to explore the key points for affacting quality. Methods The μDissTM and μFluxTM fiber-based drug solubility and permeability test systems were used to determine the solubility and permeability rate of carbamazepine APIs in different pH media, and the effective permeability was predicted.By using the intrinsic dissolution rate tablet testing device, the differences of intrinsic dissolution rate among carbamazepines from different companies and carbamazepine dehydrate were evaluated.The effects of particle sizes on the intrinsic dissolution rate were investigated by particle size analyzer, SEM and XPRD. Results Carbamazepine was a drug with low solubility, and its solubility and penetration rate were not affected by pH values.The effective permeabilities measured in pH 5.0 and pH 6.5 phosphate buffers were higher than those of metoprolol, which is a high permeable drug.There were differences in the inherent dissolution rate of APIs from different sources, and the analysis was related to particle size.In addition, the intrinsic dissolution rate of carbamazepine dihydrate was a little lower than that of carbamazepine in the same media, implying carbamazepine could be affected by the environmental humidity and turn into carbamazepine dehydrate by crystal transformation, which may lead to a decrease in the intrinsic dissolution rate. Conclusion Carbamazepine is a drug with low-solubility and high-permeability, and intrinsic dissolution rate plays an important role in in vivo absorption, which could be affected by the particle size and environmental humidity.The data support can be provided for consistency evaluation of generic drugs, by comparing the intrinsic dissolution rate of APIs from different companies.
Objective To establish the preparation of nanostructured lipid carriers as drug delivery systems using the combination of docetaxel (DTX) and photosensitive fullerene-Phenylalanine (C60-Phe) as model drugs, and to evaluate its antitumor activity against human breast cancer MCF-7 in vitro. Methods Water-soluble C60-Phe was synthesized based on the high chemical activity of C60.C60-Phe-DTX-NLC was prepared by high temperature emulsion evaporation and low temperature solidification technique, and the pharmaceutical properties were determined.The in vitro release behaviors of C60-Phe-DTX-LP were conducted by using dialysis bag method.SRB assay was used to detect the in vitro anti-tumor activity of C60-Phe-DTX-NLC on the proliferation of MCF-7 cells. Results The prepared C60-Phe-DTX-NLC morphology was spherical, and the particle size distribution was uniform.The mean particle size of C60-Phe-DTX-NLC was (136.17±3.22) nm and Zeta potential was about (-23.34±2.43) mV.And the DSC showed that DTX APIs were present in the lipid core almost amorphous.The encapsulation rate of DTX was (85.17±2.21)%, while the encapsulation rate of C60-Phe was about (93.81±1.06)%.C60-Phe-DTX-NLC had good storage stability at 4 ℃ and the cumulative release percentage of DTX within 60 h was 72.03%.The in vitro antitumor results showed that C60-Phe had antiproliferative effect aganist MCF-7 cells under 532 nm laser light exposure for 3 min.SRB results showed that C60-Phe-DTX-NLC significantly inhibited MCF-7 tumor cell proliferation when C60-Phe-DTX-NLC acted on MCF-7 cells for 6 h, then under 532 nm laser for 3 min. Conclusion The preparation process of photosensitive C60-Phe-DTX-NLC is stable and feasible, and C60-Phe-DTX-NLC shows significant anti-tumor effects in vitro.
Objective To investigate the influence of vinegar preparation process on chemical composition of Cuminum cyminum L., and to analyze the integral feature to provide a basis for its quality control. Methods HPLC was applied to determine contents of cuminaldehyde and luteolin in each Cumin sample.Fourier transform attenuated total reflection infrared spectroscopy and powder X-ray diffraction method were used to analyze the integral characteristics of each Cumin sample.X-ray fluorescence analysis method was applied to compare integral elemental contents of each Cumin sample. Results The contents of cuminaldehyde and volatile oil decreased with the increase of frying temperature and time.There was no significant change in the content of luteolin;the powder X-ray diffraction results showed that the processing technique with vinegar caused the changes on overall chemical composition of Cuminum cyminum L.;X-ray fluorescence analysis results showed that the processing technique with vinegar led to a significant reduction on the content of metal elements in Cuminum cyminum L. Conclusion The method for determining the contents of cuminaldehyde and the method for identifying the integral characteristics established in this study have broad applicability and high accuracy, and can be used to standardize and control the quality of medicinal materials of Cuminum cyminum L.using the preparation process with vinegar.
Objective To perform structural characterization and biosimilar study of herceptin and its analogues by data independent acquisition (DIA) mass spectrometry. Methods The relative molecular mass of light and heavy chains of the complete protein of herceptin and its similar drugs were determined by LC/MS.Amino acid sequences of herceptin and its biosimilar were identified using peptide mapping with DIA mass spectrometry. Results Relative molecular weights of intact and reduced herceptin and its biosimilars were detected accurately by LC/MS, and the relative molecular weight deviation between herceptin and its biosimilars was within 1 Da.DIA mass spectrometry was used to detect 106 peptides, and the amino acid sequence coverage of herceptin and its analogues was >99%.Herceptin and its biosimilar showed consistent relative molecular weights, identical amino acid sequences, and similar glycosylation profiles. Conclusion DIA mass spectrometry can be used for structure characterization and comparison study of herceptin and its biosimilar, and it can provide a basis for establishing structural characterization platform of other monoclonal antibodies in the future.
Objective To evaluate and compare in vitro antimicrobial activities of piperacillin (PIP), Piperacillin/Tazobactam (TZP), Piperacillin/Sulbactam (PIS, 2:1, 4:1), and Cefoperazone/Sulbactam (CSL, 2:1) against Gram-negative bacteria, so as to provide a reference for clinical use. Methods The minimum inhibitory concentration (MIC) of above antibacterial drugs on 6319 clinically isolated bacteria was determined by agar dilution methods recommended by Clinical and Laboratory Standards Institute (CLSI). Results PIP exhibited good in vitro activity against most non-carbapenem-resistant Enterobacteriaceae with susceptibility rates above 50% except extended-spectrum β-lactamase (ESBL)-producing Escherichia coli, ESBL-producing Klebsiella pneumoniae and Salmonella spp.TZP,PIS (2:1), and CSL exhibited potent in vitro activity against ESBL-producing E.coli,with the MIC90 values being 128/4,64/32,64/32 mg·L-1 and susceptibility rates being 75.9%, 66.2%, 72.1%, respectively.The antibacterial activity of four β-lactamase inhibitor combination formulations was poor against ESBL-producing K.pneumoniae with susceptibility rates being below 50%.CSL, PIS (2:1 and 4:1) exhibited potent in vitro activity against non-carbapenem-resistant A.baumannii, and the MIC90 values were 16/8, 16/8, 32/8 mg·L-1 and the susceptibility rates were 76.7%, 83.6%, 82.8%, respectively.Five agents exhibited potent in vitro activity against non-carbapenem-resistant P.aeruginosa, and the susceptibility rates were all higher than 80%. Conclusion The four combination formulation exhibited excellent antibacterial activity against ESBL-producing E.coli, and CSL and PIS (2:1) exhibited significant in vitro activity against non-carbapenem-resistant A.baumannii and non-carbapenem-resistant P.aeruginosa.PIS (2:1) has better antibacterial activity than PIS (4:1) against Enterobacteriaceae.PIS (2:1) and PIS (4:1) exhibited similar antibacterial activity against A.baumannii and P.aeruginosa.
Objective To systematically review the quality of the latest guidelines concerning management of chronic hepatitis B by using appraisal guidelines for research and evaluation Ⅱ (AGREE Ⅱ), so as to improve the low-quality guidelines and promote the clinical practice using high quality guidelines. Methods Databases including CNKI, WanFang Data, VIP, SinoMed, PubMed, Embase, Cocrane Library, Web of Science, and websites including CGC, Medlive, NGC, GIN, NICE, SIGN, ACPG, Google Scholar and Baidu Scholar were used to search and collect the relevant guidelines for CHB management in the past 10 years from January 1st,2011 to December 31st, 2020.The methodological quality of included guidelines was evaluated based on AGREE Ⅱ, and the differences in antiviral indications for CHB among these guidelines were compared. Results A total of 19 guidelines were included.According to AGREE Ⅱ, among 6 domains, the mean scores of “scope and purpose”, “stakeholder involvement”, “rigor of development”, “clarity and presentation”, “applicability”, “editorial independence” were 68%, 35%, 12%, 79%, 23%, and 52%, respectively.Two guidelines were graded A, and 5 guidelines were B, and 12 guidelines were C. Conclusion The overall quality of guidelines for management of CHB is not high.Great efforts are needed to develop reliable and high quality guidelines, especially for the domains of “rigor of development” and “applicability”.
Objective To evaluate the effectiveness, safety, and economy of umeclidinium/vilanterol inhalation powder (UM/VI 62.5/25 μg) based on rapid health technology assessment (HTA), so as to provide references for clinical decision-making. Methods The relevant Chinese and English databases were searched systematically.Two professionals independently screened the literature based on the inclusion and exclusion criteria.After evaluating the quality of the included literature, the extracted results were classified and descriptively evaluated. Results A total of 1 HTA report, 7 systematic reviews/Meta analysis, and 4 pharmacoeconomic studies were included.Efficacy was evaluated by the forced expiratory volume value in the first second (FEV1), St.George's Respiratory Questionnaire (SGRQ), and Transitional Dyspnea Index (TDI).UM/VI 62.5/25 μg was significantly better than placebo.Compared with glycopyrrolate/formoterol 14.4/9.6 μg, FEV1 was significantly improved (P<0.05).Compared with long acting β2 agonist/long acting muscarinic antagonist, there were improvements in FEV1, SGRQ and TDI, but there was no statistical difference.In terms of safety, compared with Tiotropium Bromide/Odaterol 5/5 μg, UM/VI 62.5/25 μg significantly increased the all-cause withdrawal rate (P<0.05).Compared with other LABA/LAMA drugs for the treatment of COPD, in terms of rescue medication use, all-cause treatment discontinuation, moderate-to-severe exacerbations, adverse events, serious adverse events, serious cardiovascular adverse events, pneumonia incidence, withdrawal due to various reasons, and all-cause mortality, there were no statistical difference.The included foreign pharmacoeconomic research showed that UM/VI 62.5/25 μg had good economic efficiency, but there was a lack of relevant pharmacoeconomic research in China. Conclusion UM/VI 62.5/25 μg has good efficacy and general safety, and it is necessary to carry out further economic evaluation research in China.
Objective To investigate the role of “instant method” in the evaluation of indoor quality control for therapeutic drug monitoring (TDM) of carbamazepine (CBZ) and to conduct pharmaceutical care analysis based on it. Methods Hospital made CBZ plasma control product with concentration of 4 μg·mL-1 were prepared.High performance liquid chromatography-ultraviolet spectrometry (HPLC-UV) method was used to determine the concentrations of CBZ and hospital-made quality control products from May 2019 to July 2020, respectively.The mean value (
Objective To explore the mode of clinical pharmacists' participating in multidisciplinary treatment (MDT) for metabolic surgery, and to evaluate the effectiveness of medication therapy management services. Methods Total 218 patients with metabolic surgery that clinical pharmacists participated in their MDT from December 2018 to December 2020 and 39 patients with metabolic surgery that clinical pharmacists did not participate in their MDT were enrolled in this study.Clinical pharmacists conducted perioperative and post-discharge medication therapy management on 218 patients through the Internet service platform.Follow-ups were conducted in the 1st, 3rd, and 6th months after management to count the number of drug treatment-related problems.The number of patients of rational rate of perioperative medications before and after management, the rate of achieving treatment goals, the incidence of adverse reactions, as well as the score and the improvement of the patient's lifestyle according to Morishy Medication Compliance Scale (MMAS)-8) were used to evaluate the implementation effect of medication therapy management. Results Total 284 drug treatment-related services were provided by clinical pharmacists.After clinical pharmacists participated in the perioperative period, the rational rate of preventive antibacterial drugs increased from <50% to >95%, and the rational rate of perioperative PPI and anticoagulant drugs use increased from 82.05% and 94.87% to both 100.00%, respectively.After 6 months of medication therapy management, the patient's understanding on the drug, poor medication compliance, and the incidence of adverse reactions decreased from 2.45, 24.31%, 12.84% to 1.48, 12.84%, 2.29%;and lifestyle improvement and treatment goal achievement rate increased from 5.50% and 63.30% to 69.27% and 99.54%, respectively. Conclusion Clinical pharmacists participate in MDT for patients with metabolic surgery to provide medication therapy management services.It can effectively improve the rational rate of perioperative drug use, patients' understanding of drugs, drug compliance and the rate of achieving treatment goals, and reduce the incidence of adverse reactions and promote rapid patient recovery.
Objective Through a case of delayed excretion caused by high-dose methotrexate in the treatment of the child with acute lymphoblastic leukemia, this paper discusses individualized treatment measures to promote clinical safety. Methods Methotrexate related drug genes were detected in a child with acute lymphoblastic leukemia.The drug genes were used to warn risks, analyze the related risk factors of delayed excretion according to the methotrexate plasma concentration, and formulate an individualized rescue plan. Results The results of drug gene test suggest that the child had the risk of delayed excretory and toxicity.The dose of methotrexate was reduced to 70% of the standard dose, and coping strategies such as hydration and alkalization were prepared in advance.After the occurrence of delayed excretory, the risk factors were found to be related to druggene, pantoprazole sodium, and kidney injury.No serious adverse reactions occurred in the child with active hydration and alkalization and dynamic adjustment of calcium folinate dose according to blood drug concentration monitoring. Conclusion High dose methotrexate was fully hydrated and alkalized in the treatment of delayed excretion in the child with acute lymphoblastic leukemia.The individualized rescue scheme was dynamically adjusted according to the blood drug concentration monitoring, so as to maintain the curative effect and avoid the accumulation of toxicity, explore individualized treatment measures, and promote clinical safety and rational drug use.
Objective To explore clinical pharmacists' participating in the treatment of pulmonary mucormycosis infection in patients with chronic renal failure. Methods Through literature study and pharmaceutical tool retrieval, clinical pharmacists took the patient's economic condition, underlying diseases, medication compliance, evidence-based medicine, and other methods into consideration, and finally worked with clinicians to formulate anti-infective regimen for the use of topical amphotericin B and monitored adverse drug reactions. Results Infusion of amphotericin B under bronchoscopy had a faster onset than the intravenous therapy with no recurrence and economic cost savings. Conclusion Clinical pharmacists participated in the treatment process of patients with chronic renal failure and pulmonary mucormycosis infection, implemented full pharmaceutical monitoring, assisted clinicians in specifying individualized treatment plans, and provided effective interventions and recommendations to improve the cure rate and reduce adverse reactions and the patient's medical economic burden.
Objective To investigate the characteristics of Guillain-Barré syndrome (GBS) adverse events related to tumor necrosis factor inhibitors (TNFis) and to mine and evaluate their risk signals, in order to provide references for the safety of drug use. Methods Data of GBS adverse event reports of etanercept, infliximab, adalimumab, certolizumab, and golimumab as the primary suspect drugs were extracted from US Food and Drug Administration Adverse Event Reporting System (FARES) between the 1st Quarter 2004 to the 1st Quarter 2020.Main characteristics of these adverse event reports were described.Risk signals were analyzed by using the reporting odds ratio (ROR) method, and a signal generated when the report numbers ≥3 and the lower limit of 95%CI of ROR>1. Results A total of 330 adverse event reports of GBS for TNFis were collected, among which 59.70% were from America and 75.76% were reported by health professionals.Females were slightly more than males, with an average age of 51.67±15.96 years old, and 56.06% of primary diseases were inflammatory lesions of arthrosis.The median GBS onset time was 248 days after receiving TNFis.Among the 330 cases, 67.58% cases were hospitalized (initial or prolonged) and 4.55% cases resulted in death.With respect to drugs, all five TNFis were reported as primary suspect drugs for GBS, while ROR analysis showed risk signals for infliximab and adamumab, and infliximab had the strongest signal [ROR 2.70, 95%CI (2.15, 3.40)]. Conclusion Analysis of FAERS data helped identify the potential risks of GBS by TNFis, which may differ among varieties.More attention should be paid to these adverse events and further pharmacovigilance is required.
Objective To explore the adverse event (ADE) signals of secukinumab and ixekizumab, and to provide a reference for the safe clinical use of two drugs. Methods The reported ratio method (ROR) and proportional report ratio method (PRR) in disproportionality analysis methods were used to mine and analyze the ADE of secukinumab and ixekizumab in FDA adverse event reporting system (FAERS) in 16 quarters from the first quarter of 2017 to the fourth quarter of 2020. Results After the calculation and secondary screening, 152 ADE signals of secukinumab and 68 ADE signals of ixekizumab were obtained, among which 15 signals were overlapping signals of secukinumab and ixekizumab.ADE signals obtained by the two drugs are basically consistent with the known safety information, mainly involving infection and infectious diseases, skin and subcutaneous tissue diseases, etc.However, it is also found that there are some incompleteness in drug instructions and differences between ADE and ADE, which suggest that we should pay attention to the selection of drugs according to individual conditions of patients. Conclusion Based on FAERS database, the ADE signals of secukinumab and ixekizumab after marketing are mined and analyzed, which can provide a reference for drug safety in clinical practice.
In accordance with the relevant requirements of the current version of “Good Clinical Practice”(GCP), combined with the relevant requirements for quality management, risk management and risk-based quality management issued both domestic and international, taking the introduction of the risk management strategy to the quality management system of drug clinical trial institution as the entry point, the quality risk points that may be involved in the entire process of clinical trials were identified, analyzed and evaluated.Corresponding risk response measures for different risk levels were proposed.Given full play to the role of risk management strategies in the quality management of clinical trial institutions, the efficiency of clinical trial quality management was improved, and the study will provide a reference for drug clinical trial institutions to carry out quality management work.
Objective To evaluate the application of PDCA (Plan-Do-Check-Action) cycles to the management of antibiotic combinations in a hospital. Methods The situation of antibiotic combinations therapy in a hospital was investigated from January to December of 2019.PDCA method was used to conduct clinical pharmacist-led management of antibiotic combinations from July to December of 2020.The proportion of antibiotic combinations,the cost of antibiotics use and intensity,and other related indicators before and after intervention were compared. Results After a series of intervention measures led by clinical pharmacists,the related assessment indexes of antibiotics combination management were statistically significant compared with those in before (P<0.05).The proportion of antibiotic combinations decreased by 53.1%,among which the proportions of dual,triple,and quadruple combination of antibiotics decreased by 48.81%,68.41%,and 77.90%,respectively.The amount of costing and intensity of antibiotics used decreased by 23.4% and 6.39%,and the number of adverse drug antibiotics related reactions decreased by 37.3%.Under the guidance of the medical department and the support of the clinical departments,a control system of antibiotic combinations management led by clinical pharmacists was established by scientifically setting the target value of antibacterial drug intensity,innovating the antibiotic medical order review module,and establishing review system for antibiotic prescriptions in key departments. Conclusion Using PDCA method,clinical pharmacist antibiotic combinations management has reduced the proportion and unreasonable antibiotic combinations,which improved the level of rational use of antibiotics in our hospital.