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AIM: To compare the efficacy of different dosing regimens of conbercept in the treatment of pathological myopic choroidal neovascularization(CNV).METHODS: Prospective clinical study. Totally 42 patients(42 eyes)who were diagnosed with pathological myopic CNV in our hospital from January 2019 to January 2022 were selected in the study. According to two different initial dosing regimens, the patients were divided into 1+pro re nata(PRN)group, with 20 patients(20 eyes), and 3+PRN group with 22 patients(22 eyes). The patients in the 1+PRN group were given one intravitreal injection and then given PRN, the patients in the 3+PRN group were given intravitreal injection once a month for 3 mo and then given PRN. Followed-up for 12 mo after initial treatment, the best corrected visual acuity(BCVA), central macular thickness(CMT), CNV area and injection times were compared between the two groups.RESULTS: The BCVA was improved, CMT was decreased, and CNV area was reduced at 1, 3, 6, and 12 mo after the initial treatment(P<0.01). However, there was no statistically significant difference in BCVA, CMT and CNV area between two groups(P>0.05). The average injection in the 1+PRN group was significantly less than that of the 3+PRN group [2(1, 3)times vs 3(3, 4)times, P<0.05], but the average reinjection in the 1+PRN group was more than that of the 3+PRN group [1(0, 2)times vs 0(0, 1)times, P<0.05].CONCLUSION: Two regimens were both safe and effective in the treatment of pathological myopic CNV by Conbercept, which can improve BCVA, decrease CMT, and reduce CNV area, with less total times of injection in the 1+PRN regimen, and less times of reinjection in the 3+PRN regimen.
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Buccal tablets
Diclofenac sodium
Drug release
Mucoadhesion
Mucoadhesive tablets
Release kinetics
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Objective:To investigate the efficacy and adverse reactions of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with chemotherapy in the treatment of superior mediastinal lymph node metastasis after esophageal cancer surgery.Methods:The clinical data of 72 patients with concurrent chemoradiotherapy for superior mediastinal lymph node metastasis after esophageal cancer surgery in Tai'an Cancer Prevention and Treatment Hospital from January 2019 to May 2021 were retrospectively analyzed, and they were divided into intensity-modulated radiotherapy (IMRT) group (36 cases) and SIB-IMRT group (36 cases) according to different radiotherapy methods. The short-term efficacy, long-term survival rate and adverse reactions of the two groups were compared.Results:The response rate in the IMRT group was 66.7% (24/36), the response rate in the SIB-IMRT group was 86.1% (31/36), and the difference between the two groups was statistically significant ( χ2 = 3.77, P = 0.047). The 1-, 2- and 3-year overall survival rates in the IMRT group were 75.0%, 44.4% and 27.8%, and the 1-, 2- and 3-year overall survival rates in the SIB-IMRT group were 83.3%, 52.8% and 33.3%; the difference in the overall survival between the two groups was not statistically significant ( χ2 = 0.70, P = 0.401). There were statistical differences in the incidence of leukopenia, radiation esophagitis and radiation pleural gastritis between the two groups (all P < 0.05). There were no statistical differences in the incidence of radiation pneumonia and gastrointestinal reactions between the two groups (both P > 0.05). Conclusions:SIB-IMRT combined with chemotherapy in patients with superior mediastinal lymph node metastasis after esophageal cancer surgery has good local control rate and mild adverse reactions.
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New drug clinical trials have been considered as a positive way for treating cancer by cancer patients and doctors, and the extended dosing is a special way for patients' withdrawal from antitumor clinical trials to obtain investigational new drugs. However, neither the regulations of expanded dosing nor the detail documents for expanded dosing have been officially published in China. At present, expanded dosing of investigational drugs is still at the exploratory stage in various medical institutions, and a complete management system has not been established to meet patients' urgent needs for drug use. Based on the practical experience of extended dosing in Hunan Cancer Hospital, this paper preliminarily explored the application procedures and ethical review requirements of extended dosing for subjects in antitumor clinical trials. It is necessary to clarify the responsibilities of all patients in the procedure and establish a patient-medical institution-sponsor joint application system. In the process of ethical review, it is recommended that all parties fully consider the risks and benefits of extended dosing for patients, and then the ethics committee makes a comprehensive assessment to decide whether to approve extended dosing.
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Humains , Chine , Médecins , Antinéoplasiques/usage thérapeutiqueRésumé
Objective:To investigate the effects of Tiaogan Lifei Decoction on the level of symptom control in patients with bronchial asthma (asthma) treated with moderate and high dosage inhaled glucocorticoids (ICS).Methods:Randomized double-blind placebo controlled prospective study was used. Totally 90 patients with asthma (liver lung disharmony, wind phlegm blocking collateral syndrome) using moderate and high dosage ICS who met the inclusion criteria from January 2020 to December 2021 in Chaoyang District Hospital of Traditional Chinese Medicine in Beijing were divided into two groups according to random number table method, with 45 cases in each group. On the basis of using the original dosage of ICS, the treatment group used Tiaogan Lifei Decoction, while the control group used Tiaogan Lifei Decoction simulant. The course of treatment was 12 weeks. TCM symptom score of both group before and after the treatment was detected; asthma control test (ACT) was used to assess the effects of asthma on the patients; St George's Hospital Respiratory Questionnaire (SGRQ) was used to assess patients' quality of life; the peak expiratory flow rate (PEF) was measured with a peak expiratory flow meter. 2 ml of venous blood was collected for eosinophil (EOS) detection, and the serum allergen specific IgE level was determined by ELISA. The adverse reactions were observed during the treatment and the clinical efficacy was evaluated.Results:During the test, 3 cases and 2 cases in the treatment group and control group lost prevention respectively. 3 cases in the treatment group and 6 cases in the control group withdrew from the trial because of the aggravation of symptoms and the need to increase the dosage of ICS. The total effective rate in the treatment group was 78.6% (33/42), and that in the control group was 55.8% (24/43), with statistical significance ( χ2=4.98, P=0.026). After treatment, the scores of daily activities, early awakening, control and total scores in the treatment group were higher than those in the control group ( t values were 1.76, 1.99, 2.00, 2.69, respectively, P<0.01 or P<0.05); after treatment, the scores of cough, chest tightness, active wheezing, upset, pharyngeal itch and total score in the treatment group were lower than those in the control group ( t values were -5.89, -6.01, -5.66, -4.27, -6.67, -9.05, respectively, P<0.01); SGRQ score in the treatment group was lower than that of the control group ( t=-7.19, P<0.01). No serious adverse reactions occurred during treatment in the two groups. Conclusion:Tiaogan Lifei Decoction is helpful to improve the symptom control level of asthma patients who are using ICS, and effectively improve the quality of life of patients with asthma of liver lung disharmony and wind phlegm obstructing collaterals syndrome.
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OBJECTIVE To investigate the effects of individualized dosing regimen on blood trough concentration of vancomycin and renal function in critically ill patients. METHODS According to relevant guidelines and the results of Vancomycin Calculator, clinical pharmacists formulated an individualized dosing regimen of vancomycin including loading dose and maintenance dose for critically ill patients based on the two independent variables of body weight and creatinine clearance rate. Using the method of retrospective study, patients who were admitted to the department of intensive care unit (ICU) of the Second Affiliated Hospital of Guangzhou Medical University and used the regimen from July 2018 to December 2021 were selected as the trial group, and patients who were treated with vancomycin and received blood drug concentration monitoring in ICU from January 2015 to June 2018 were recruited in the control group. The difference in trough concentration distribution and the incidence of acute kidney injury (AKI) after medication were compared between the two groups, the change of serum creatinine before and after medication in the trial group was analyzed. RESULTS Totally 197 patients were included in the trial group and 144 patients were in the control group. There was no significant difference between the two groups in the clinical information (gender, age, body weight, acute physiology and chronic health evaluation Ⅱ score, the proportion of patients with renal insufficiency, etc.) (P>0.05). The proportions of major infection sites (including lung, urinary, abdominal, blood and central nervous system) and treatment type (target or empirical treatment) also had no significant difference between the two groups (P>0.05). There was no significant difference in the attainment rate of ideal trough concentration (15-20 μg/mL) and the proportion of patients with trough concentration >20 μg/mL between the two groups (P>0.05), while the attainment rate of target trough concentration (10-20 μg/mL) and the proportion of patients with trough concentration <10 μg/mL were significantly different between the two groups (P<0.05). The attainment rate of target trough concentration in patients with chronic renal insufficiency in trial group was significantly higher than that in control group (P<0.05). There was no significant difference in the incidence of AKI and vancomycin-associated AKI between the two groups (P>0.05). In the trial group with medication duration ≥7 days , the level of serum creatinine on the 7th day of treatment was increased significantly, compared with that on the 3rd day of treatment (P<0.05). CONCLUSIONS This individualized dosing regimen can improve the attainment rate of target trough concentration of vancomycin in critically ill patients, especially those with chronic renal insufficiency, during the first standardized monitoring, and not increase the risk of renal injury compared with previous empirical medication.
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Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.
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Pharmacokinetics/pharmacodynamics study fully considers the relationship among pathogens, hosts and drugs, which reflects the relationship between bactericidal effects and adverse drug reactions and the change of drug concentrations, which is of much value to the rational use of antimicrobial agents and delaying antimicrobial resistance.This review discussed design and optimization of dosing regimens for anti-infective therapy base on theory of pharmacokinetics/pharmacodynamics.
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Objective:To compare the clinical efficacy and safety of continuous dosing or alternate-day dosing of apatinib combined with SOX regimen as first-line treatment for patients with advanced gastric cancer.Methods:A total of 52 patients with human epidermal growth factor receptor 2 (HER2) negative and inoperable locally advanced or advanced gastric cancer who were pathologically diagnosed from January 2018 to January 2021 in the Second Affiliated Hospital of Shandong First Medical University were collected. The patients were divided into continuous dosing group and alternate-day dosing group by random number table method. The continuous dosing group received apatinib (250 mg, once a day) combined with SOX regimen (S-1+oxaliplatin); the alternate-day dosing group received apatinib (250 mg, once every other day) combined with SOX regimen. Twenty-one days were a cycle, and the efficacy was evaluated after 2 cycles. After 4-6 cycles, patients with stable disease received apatinib and S-1 for maintenance therapy. The therapeutic effects and adverse reactions of the two groups were compared.Results:The curative effect could be evaluated in 51 patients, including 26 in the continuous dosing group and 25 in the alternate-day dosing group. The disease control rates in the continuous dosing group and the alternate-day dosing group were 84.6% (22/26) and 76.0% (19/25) ( χ2 = 0.60, P = 0.499), and the median progression-free survival time was 7.50 months (95% CI 6.17-8.83 months) and 8.30 months (95% CI 6.99-9.61 months) ( χ2 = 0.71, P = 0.401), and the median overall survival time was 15.50 months (95% CI 11.30-19.69 months) and 15.60 months (95% CI 13.63-17.57 months) ( χ2 = 1.82, P = 0.177). The main adverse reactions in the two groups were leukopenia, thrombocytopenia, hypertension, nausea, vomiting, fatigue, hand-foot syndrome, proteinuria, liver and kidney damage. The incidence rates of ≥grade 3 adverse reactions in the continuous dosing group and the alternate-day dosing group were 42.3% (11/26) and 12.0% (3/25), and the difference was statistically significant ( χ2 = 4.46, P = 0.035). Conclusions:The efficacy of continuous dosing or alternate-day dosing of apatinib combined with SOX regimen as first-line treatment for advanced gastric cancer is similar, but the incidence of ≥grade 3 adverse reactions in alternate-day dosing group is lower, which improves the compliance and tolerance of patients.
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Resumen Los antimicrobianos corresponden al grupo de medicamentos más utilizados en Unidades de Cuidados Intensivos Neonatales; no obstante, su uso ha sido asociado a constantes errores de medicación en la práctica clínica. Paradojalmente, aún no existe consenso en torno a la administración adecuada de estos medicamentos y existen importantes brechas de conocimiento en torno a los procesos de dosificación, administración y manipulación de antimicrobianos en esta población. Con el fin de mejorar el uso de antimicrobianos, disminuir errores y optimizar los resultados clínicos en el recién nacido, la presente revisión tiene por objetivo entregar recomendaciones y servir de guía para la correcta preparación de aquellos antimicrobianos de mayor relevancia en neonatología.
Abstract Antimicrobials are among the most commonly prescribed classes of medications in Neonatal Intensive Care Units; however, its use has been constantly associated with a number of medication errors in clinical practice. In contrast to this situation, there is no common agreement when it comes to determining the right dosing, administration, or handling of antibiotics in this population. In order to help improve the use of antibiotics, decrease the rate of medication errors and optimize clinical results in the newborn, this review aims to provide recommendations to support and guide the correct preparation of some of the most relevant antibiotics used in neonatal wards.
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Humains , Nouveau-né , Antibactériens/administration et posologie , Néonatologie , Unités de soins intensifs néonatals , Hôpitaux , Erreurs de médication/prévention et contrôleRésumé
Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.
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AIM: To study the polymorphism distribution of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes and their influence on serum homocysteine (Hcy) concentration. METHODS: A total of 148 patients diagnosed with ischemic stroke from November 2020 to February 2021 in Yijishan Hospital of Wanan Medical College were selected for the study, and patients were typed for MTHFR 677C/T and MTRR 66A/G genes using fluorescent staining in situ hybridization technique. Serum Hcy concentrations were measured in 21 patients using a circulating enzyme assay. The distribution of MTHFR 677C/T and MTRR 66A/G gene polymorphisms were analyzed, and the differences in serum Hcy concentrations between patients with different genotypes were compared. RESULTS: The mutation rates of MTHFR 677C/T and MTRR 66A/G genes were 42.57% and 26.01%, respectively, and no significant differences in gene distribution frequencies were observed between men and women (P>0.05). The mean Hcy serum concentration was (16.04±4.34) μmol/L in 21 patients, including 8 patients (38.10%) with 0.05). CONCLUSION: MTHFR gene polymorphisms can affect serum Hcy concentrations. The MTHFR genotyping can be considered for individualized folic acid supplement. This conclusion should be further verified by expanding the clinical sample size.
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AIM: To develop software for individualizing dosage regimens of vancomycin (VCM) according to the established population pharmacokinetics (PPK) models. METHODS: VCM dosing software was developed using MyEclipse, SQL Server, and JRE. The software developing schemes included requirement analysis, general design, detailed design, software coding, software test, software maintenance and software redevelopment. RESULTS: The developed software achieved the functions such as input and management of patient information, prediction of trough concentrations under various dosing regimens which could help initial dosage design, and prediction of trough concentrations more accurately based on therapeutic drug monitoring results and Bayesian method which could help dosage adjustment. The software was utilized in the interpretation of VCM serum concentration, pharmacists proposed the suggestions for adjusting dosage regimens. The rechecked serum concentrations all reached the expected target blood concentration range in the group of adopting advice. CONCLUSION: The new developed software based on our established PPK models can provide a useful tool in the clinical setting to facilitate the individualized therapy for the adult and elderly infected patients.
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The appropriate dosing regimens of secukinumab for psoriatic arthritis (PsA) are not well defined. We performed a meta-analysis to evaluate the efficacy and safety of different dosing regimens of secukinumab in the treatment of PsA. A systematic search was conducted using major electronic databases to identify relevant randomized controlled trials (RCTs) comparing secukinumab 300 mg versus secukinumab 150 mg in patients with PsA. Meta-analysis was performed using Review Manager software (version 5.3). Six studies with a total of 1141 patients were included. At week 24, secukinumab 300 mg was associated with a higher American College of Rheumatology 20% response (ACR 20), ACR 50, PASI 75 response rate, and dactylitis resolution rate than secukinumab 150 mg, especially in the anti-TNF-IR subgroup. At week 52, secukinumab 300 mg was associated with a higher psoriasis area and severity index (PASI) 75 and PASI 90 response rate than secukinumab 150 mg. There was no significant difference between secukinumab 300 mg and secukinumab 150 mg in the risk of any adverse events (AEs) and serious AEs at either week 24 or week 52. Secukinumab 300 mg was significantly more effective than 150 mg, especially for patients with PsA who have failed TNF therapy, and it was well tolerated.
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Humains , Psoriasis , Arthrite psoriasique/traitement médicamenteux , Indice de gravité de la maladie , Résultat thérapeutique , Anticorps monoclonaux humanisés , Anticorps monoclonaux/effets indésirablesRésumé
RESUMEN El descubrimiento de que la síntesis de 1,25 vitamina D no fue solo renal, la enzima 1 alfa hidroxilasa se encuentra en numerosos tejidos del organismo, además de la evidencia de que la asociación entre el déficit de vitamina D y la presencia de enfermedades no óseas (cáncer, esclerosis múltiple, enfermedades autoinmunes, etc.) nos ofrece la posibilidad de intentar prevenir estas afecciones. Los estudios de suplementación contra placebo no han dado resultados positivos para algunas afecciones, aunque algunos de esos trials se realizaron en población "suficiente" y no "deficiente" de vitamina D. Sin embargo, otros metaanálisis han demostrado prevención en los grupos suplementados con déficit para algunas patologías (infecciones respiratorias, prediabetes). Además, existe evidencia de efecto antiviral de la misma. La acción antiinfecciosa e inmunomoduladora que ejerce y su efecto sobre el sistema renina angiotensina, estimulando la enzima convertidora de angiotensina 2 (que es el receptor virus del SARS-CoV), permiten sospechar, actualmente, que con niveles elevados podría ser más difícil, o menos grave, la infección por COVID-19. La suplementación con vitamina D es conveniente para prevenir enfermedades en sujetos con déficit, pero en medio de la grave pandemia 2020 administrarla, aún sin tener un dosaje previo en las poblaciones de mayor riesgo, podría disminuir la chance de esta enfermedad.
ABSTRACT The discovery that the synthesis of 1-25-vitamin D is not only renal and that the enzyme 1 alpha hydroxylase is found in numerous tissues of the body, together with the evidence of the association between vitamin D deficiency and the presence of non-bone diseases (cancer, multiple sclerosis, autoimmune diseases, etc.), gives us the possibility of trying to prevent these conditions. Placebo-controlled supplementation studies have not provided positive results for certain conditions, but some of these trials have been carried out on populations with "sufficient" and not "deficient" vitamin D levels. However, other meta-analyses have shown prevention of some conditions (respiratory infections, prediabetes) in groups of patients with deficiencies who were given supplements. There is also evidence of antiviral effect of vitamin D. Its anti-infective and immunomodulatory action and its effect upon the renin-angiotensin system, stimulating the angiotensin-converting enzyme 2 (the SARS-CoV virus receptor), nowadays allow us to think that, in high levels, COVID-19 infection could be less likely or serious. Vitamin D supplementation is adequate for preventing diseases in patients with deficiencies; administering vitamin D within the 2020 pandemic, even without having tested it in high-risk populations, could diminish the incidence of this disease.
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Resumen Los antimicrobianos son los medicamentos más utilizados en los neonatos durante su primer mes de vida cuando se encuentran en unidades neonatales, principalmente por el alto riesgo que presentan de adquirir infecciones graves como la sepsis. La mayoría de estos antimicrobianos se utilizan con dosis extrapoladas en base a las recomendaciones en población adulta y niños mayores, a pesar de que la fisiopatología en los recién nacidos es absolutamente diferente. Lo anterior lleva a un mayor riesgo a que ocurran más efectos adversos los que pueden conducir a una mayor toxicidad y a fallas terapéuticas, entre otros. En la última década se han realizado mayores estudios farmacocinéticos de antimicrobianos en neonatos; esta reciente evidencia ha permitido nuevas recomendaciones de dosificación considerando el peso y la edad gestacional del recién nacido, entre otras variables, de acuerdo al antimicrobiano estudiado. En base a una mayor evidencia sobre el comportamiento farmacocinético de los antimicrobianos en neonatos, se ha elaborado este documento para así facilitar y promover su correcto uso en las unidades neonatales.
Abstract Antibiotics are the most widely used medications in neonates during their first month of life in neonatal units, mainly due to the high risk they present of acquiring serious infections such as sepsis. Most of these antibiotics are used with extrapolated doses based on the suggestions in the adult population and older children, despite the fact that the pathophysiology in newborns is absolutely different. This leads to a higher risk of more adverse effects occurring, which can lead to greater toxicity and therapeutic failures, among others. In the last decade more and more pharmacokinetic studies of antibiotics have been carried out in neonates, this recent evidence has led to new dosage recommendations taking into account the weight and gestational age of the newborn, among other variables, in agreement to the antibiotic studied. Therefore, based on the need to order and summarize the most up-to-date and most evidence-based information on antibiotics in neonates, this document was prepared to facilitate and promote its correct use in neonatal units.
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Humains , Nouveau-né , Maladies transmissibles , Antibactériens/usage thérapeutique , Néonatologie , Chili , Comités consultatifsRésumé
OBJECTIVE:To introduce the development and application of automatic dosing and mixing system of intravenous infusion in PIVAS of our hospital. METHODS :Based on the bar code management system in PIVAS ,combined with automatic mixing equipment ,our hospital developed and designed automatic dosing and mixing system of intravenous infusion which could realize real-time scanning and charging of drugs ,setting parameters of mixed dispensing and automatic dosing and mixed dispensing of intravenous infusion. Compared with manual dispensing model ,work efficiency of 5 staff who dispensed Coenzyme complex for injection and Carbazochrome sodium s ulfonate for injection 300 bags each as well as the amount of drug residues in empty bottle were investigated to evaluate the effects of the system. RESULTS :The system realized automatic mixing of intravenous infusion. In manual dispensing model and automatic dispensing model ,the mixing efficiency of Coenzyme complex for injection were (96.6±10.0)and(195.2±10.7)bag/h(P<0.001);mixing efficiency of Carbazochrome sodium sulfonate for injection were (83.8±12.9)and(118.8±6.7)bag/h(P<0.001). The amount of residual liquid in Coenzyme complex for injection empty bottle were (0.09±0.02)and(0.11±0.01)mL;Carbazochrome sodium sulfonate for injection empty bottle were (0.08± 0.02)and(0.12±0.01)mL,which were all lower than the internal control requirements that injected solvent volume was no more than 5% (0.15 mL). CONCLUSIONS :The automatic dosing and mixing system of intravenous infusion could improve the efficiency of intravenous infusion dispensing and reduce the labor intensity of the staff .
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Chloroquine (CQ) phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019 (COVID-19). To develop a physiologically-based pharmacokinetic (PBPK) model for predicting tissue distribution of CQ and apply it to optimize dosage regimens, a PBPK model, with parameterization of drug distribution extrapolated from animal data, was developed to predict human tissue distribution of CQ. The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism. Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships. The model was also validated by clinical data from Chinese patients with COVID-19. The novel PBPK model allows in-depth description of the pharmacokinetics of CQ in several key organs (lung, heart, liver, and kidney), and was applied to design dosing strategies in patients with acute COVID-19 (Day 1: 750 mg BID, Days 2-5: 500 mg BID, CQ phosphate), patients with moderate COVID-19 (Day 1: 750 mg and 500 mg, Days 2-3: 500 mg BID, Days 4-5: 250 mg BID, CQ phosphate), and other vulnerable populations (.., renal and hepatic impairment and elderly patients, Days 1-5: 250 mg BID, CQ phosphate). A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.
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AIM: To design and implement personalized dosing regimens of trastuzumab and pertuzumab for an Asian patient with early breast cancer. METHODS: Trastuzumab and pertuzumab are important therapeutics for patients with HER2-positive breast cancer. Despite the similar pharmacokinetics (PK), their recommended dosing regimens differ: pertuzumab dosing is fixed whereas trastuzumab dosing depends on body weight; the dosing frequency is once every three weeks for pertuzumab but includes both once every week (QW) and once every three weeks (Q3W) for trastuzumab. A practicing physician has limited choices for dosing regimens when using the drugs in combination with chemotherapies. Besides convenience in drug administration, efficacy and safety as responses to the drug must be examined as part of studying dose-exposure-response relationship, which is the basis for deciding a dosing regimen. To understand the dose-exposure-response relationship of an individual patient, we reviewed literature on population PK analyses. The associated PK-covariate relationships including influential covariates such as disease status and demographics (e.g., body weight) that informed the patient's underlying dose-exposure-response relationships. Safety and efficacy factors essential for choosing appropriate dosing regimens were also considered - minimal target concentrations, higher adverse event rates in Asian patients, as well as administration convenience. RESULTS:Based on a thorough review of population PK and PK-covariate relationships of pertuzumab and trastuzumab, an individualized dosing regimen of once every two weeks (Q2W) was selected as the treatment option and implemented for this patient. CONCLUSION: The design of an individualized dosing regimen requires the knowledge of individualized dose-exposure-response relationships, and population analysis is an ideal tool for understanding the individualized dose-exposure-response relationships.
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Background: Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit with considerable psychosocial impact. Oral azithromycin or oral doxycycline can be used for the management of moderate and severe acne vulgaris. However, there is no consensus on which antibiotic is superior and the optimal dose for management.Methods: A prospective randomized interventional study was carried out among 120 patients of moderate to severe acne vulgaris. The patients were randomized into group A and B. While group A was prescribed oral azithromycin 500 mg three times a week, group B was given oral doxycycline 100 mg daily for 12 weeks. Topical clindamycin twice daily application was also given. Global Acne Grading Scale (GAGS) score was recorded at baseline and at 2nd, 4th, 8th and 12th weeks.Results: GAGS score at baseline in azithromycin (n = 53) and doxycycline (n = 55) group was 31.98±4.49 and 30.63±3.78 respectively (p value >0.05). 83.91±6.83% (p <0.001) and 81.87±6.75% (p <0.001) improvement was seen in azithromycin group and doxycycline group after 12 weeks of treatment. However, there was no difference in the GAGS score between the groups at any follow-up (p value >0.05). 15.09% patients in azithromycin group and 20% patients in doxycycline group reported adverse effects. The most commonly reported adverse effect was diarrhoea. All adverse effects were of ‘mild’ category and causality assessment was ‘possible’.Conclusions: Oral azithromycin is equally efficacious but safer alternative to oral doxycycline for the management of acne vulgaris.