Application progress on in vivo drug analysis technique in clinical pharmacy / 药学实践杂志

Objective To explore the progress on the application of in vivo drug analysis techniques in clinical pharmacy work. Methods Relevant literature was reviewed to provide an overview of the characteristics of clinical samples, common in vivo drug analysis methods used in the clinic, the application and existing problems of in vivo drug analysis in clinical pharmacy. Results and Conclusion In recent years, with the increasing demand for individualized and precise treatment in clinical practice and the continuous development of analytical techniques, in vivo drug analysis techniques have been widely used in clinical pharmacy work, which have become one of the important auxiliary techniques to promote rational clinical drug use, improve individualized treatment and reduce the occurrence of adverse reactions. However, in the actual application, there were still problems such as the invasive blood sampling that hinders sampling, the weak ability to interpret drug monitoring results and clinical testing methods that still need to be improved. These problems should be taken seriously and continuously improved and solved in the subsequent research and application.

Research progress in therapy drug monitoring of levetiracetam / 中国药房

Levetiracetam （LEV） is the second generation of broad-spectrum anti-epileptic drug. LEV has the advantages of rapid absorption， short half-life， precise efficacy， good tolerance and few drug interactions. In order to improve the clinical efficacy of LEV， and reduce the occurrence of adverse reactions， children， pregnant women， the elderly， and patients with renal insufficiency should receive therapeutic drug monitoring （TDM）. Clinically， the samples are usually plasma or serum， and the TDM methods are mostly immunoassay or chromatography. There is currently no consensus on the effective concentration range of LEV， and the correlation between plasma concentration and adverse reactions is also unclear. The main factors affecting LEV plasma concentration include age， pregnancy， and patient compliance. How to interpret TDM results and adjust dosage based on the results will be the focus of future work.

Investigation of patients’preferences regarding therapeutic drug monitoring of mycophenolic acid in solid organ transplantation / 中国药房

OBJECTIVE To investigate the preferences of patients who underwent solid organ transplantation regarding therapeutic drug monitoring （TDM） of mycophenolic acid （MPA） and explore the factors influencing patients’ decision-making process， so as to provide support for the development of individualized medication guidelines for MPA and improvement of clinical decision-making. METHODS The cross-sectional study was used to design the questionnaire on the patients’ preferences to accept MPA TDM， and involved patients who underwent solid organ transplantation and received MPA treatment at two tertiary hospitals in Beijing from April 14， 2022， to June 27， 2022. The Likert 5-level scoring method was used to score the patients’ preferences to accept MPA TDM， the influencing factors and their correlation of the patients’ preferences to accept MPA TDM were analyzed by Pearson correlation analysis and binary Logistic regression analysis， and the nonparametric test and chi-square test were used to rank and analyze the consistency of the factors affecting patients’ preference decision. RESULTS A total of 140 questionnaires were collected， and the effective recovery rate was 77.35%. The average preference score of 140 patients to receive MPA TDM was （4.01±0.65）， and the overall preference value was high. There were 116 （82.86%） patients agreed or strongly agreed with MPA TDM. Significant differences were observed in preference scores between patients who had previously undergone MPA TDM and those who had never undergone it （[ 4.30±0.53） scores vs. （3.80±0.65） scores， P＜0.001]. Additionally， patients’ preference scores were significantly influenced by their understanding level and attention level （P＜0.001）. The ranking of factors contributing to decision-making exhibited consistency （P＜0.001）. The factors were ranked in descending order of clinical efficacy， safety， comfortability， economy and time cost. CONCLUSIONS The patients who underwent solid organ transplantation hold high preferences towards MPA TDM. The primary factors influencing their decisions are their prior experience， understanding level， and attention level.

Quality evaluation of Chinese and global guidelines/consensus for TDM of anti-TNF-α agents in patients with inflammatory bowel disease / 中国药房

OBJECTIVE To evaluate the quality of guidelines/consensus on therapeutic drug monitoring （TDM） of anti-tumor necrosis factor-α （TNF-α） in patients with inflammatory bowel disease （IBD） in China and globally. METHODS PubMed， Embase， CNKI， Wanfang data， VIP， and release websites of guidelines/consensus in China and globally were searched to collect guidelines/expert consensus on TDM with anti-TNF-α for IBD patients. The search period was from database establishment to June 2023. After two investigators independently screened the literature and extracted the data， the methodological quality of the included guidelines/consensuses was evaluated using the Appraisal of Guidelines for Research and Evaluation Ⅱ. The main recommendations of the included guidelines/consensuses were summarized. RESULTS A total of 9 articles were included， 3 were guidelines and 6 were expert consensus. The standardized percentages of the 9 guidelines/consensus in the 6 dimensions （scope and aims， participants， rigor of formulation， clarity of expression， application， and editorial independence） were 90.43%， 41.98%， 52.55%， 85.49%， 19.00%， and 76.85%， respectively. Eight guidelines/consensus had a recommendation of grade B and one consensus of grade C. The main recommendations involve TDM application scenarios， threshold ranges， strategy adjustments， detection methods， and interpretation of results. Most guidelines/consensus recommend passive TDM for non-responders. It is recommended to set the TDM concentration range according to the expected treatment results and make strategy adjustments in combination with the disease condition and TDM results. Additionally， the same test method is recommended for the same patient. Some guidelines/consensus hold that no differences were noted in the interpretation of results between biosimilar and original drug. CONCLUSIONS The overall quality of the included guidelines/consensus was fair， with relatively consistent recommendation. Clinicians need to understand the characteristics and limitations of TDM with this class of drugs， and interpret and apply results of TDM in combination with specific clinical treatment goals.

Evaluation of proactive therapeutic drug monitoring application in infliximab users in ulcerative colitis

Objective: To evaluate the application of proactive pro-drug therapy (TDM) at week six in users of infliximab therapy in ulcerative colitis patients and to analyze the need for further disease optimization. Method: This is a retrospective analysis that will be carried out simultaneously at the Hospital de Clínicas de Passo Fundo and at the Endoclin Diagnostic Center in the city of Passo Fundo, with secondary data collection between January 2020 and May 2022. The sample included patients from both sexes, regardless of age, who are being followed up in the services mentioned above, by signing the informed Free and Clarified Consent Term. Results: 63.2% of patients required optimization of their treatment based on the serum level assessment at week six. Conclusion: Proactive TDM performed at week six benefits patients in order to complete indications for treatment to avoid lack of drug response and complications from the disease. (AU)

Therapeutic drug monitoring in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a problem that directly affects the quality of life of patients suffering from this condition. Monitoring the serum level of infliximab (IFX) (TDM) is an important tool for guiding therapeutic decisions in IBD patients. The purpose of this study was to determine the significance of quantitatively measuring the serum level of IFX (TDM) and antibody to IFX (ATI). Methods and materials: Prospective observational study involving 40 IBD patients on IFX therapy, including 14 Proactive (week 06 of the induction phase) and 26 Reactive (maintenance phase). Immediately prior to the infusion, blood samples were drawn and measured using a Bulhlmann rapid test instrument. Serum concentrations of IFX were categorized as supratherapeutic (>7.0 micrograms/ml), therapeutic (between 3.0 and 7.0 micrograms/ml), and subtherapeutic (3.0 micrograms/ml). When the serum concentration of IFX was 3 mcg/ml (subtherapeutic), the ATI was measured. 25 patients with CD and 15 patients with UC were evaluated. Only three of the twenty patients with subtherapeutic serum levels had a positive ATI, and both were reactive; two had CD and one had UC. There was a statistically significant difference between reactive and proactive patients with respect to levels of CRP (p = 0.042), with proactive DNS patients suffering greater alterations in CRP and albumin. (AU)

Influence of sex on the exposure to isoniazid in patients with pulmonary tuberculosis

ABSTRACT Isoniazid is a key component of tuberculosis treatment. Adequate exposure is a determinant for therapeutic success; however, considerable inter- and intraindividual variations in drug plasma levels can lead to unfavorable outcomes. While some predictors of isoniazid levels are well-known, others, such as sex, yield controversial results, requiring further investigation to optimize exposure. This study investigates whether the sex of patients influences the dose administered and the concentrations of isoniazid in plasma. Levels of isoniazid were associated with the N-acetyltransferase 2 phenotypes. A total of 76 male and 58 female patients were included. Isoniazid was measured by high-performance liquid chromatography, and N-acetyltransferase 2 phenotypes were assessed using molecular techniques. The results show that the dose administered, expressed in mg/kg, was higher in females, but the plasma levels were similar between both sexes. Among patients, 46.2%, 38.8%, and 15% were slow, intermediate, and fast acetylators, respectively. As expected, isoniazid levels were associated with the acetylation phenotypes, with higher concentrations in the slow acetylators. Thus, sex-related difference in isoniazid levels is due to the body weight of patients, and the optimized dose regimen based on patient weight and acetylator phenotypes can improve the treatment outcomes.

A retrospective analysis to estimate trough concentrations of teicoplanin in patients with suspected or documented Gram-positive infections

Abstract Teicoplanin is a glycopeptide antibiotic commonly used to treat Gram-positive bacterial infections in the clinic. The aim of this study was to provide a therapeutic reference for the clinical application and dosage regimen adjustment of teicoplanin by identifying factors associated with its plasma trough concentration (Ctrough). A retrospective study was performed on patients with suspected or documented Gram-positive infections who were hospitalized from November 2017 to January 2020 and treated with teicoplanin while undergoing routine therapeutic drug monitoring (TDM). A total of 112 Ctrough trough measurements were obtained from 72 patients were included in this study. SPSS software was used for correlation analysis and receiver operator characteristic curve (ROC) analysis. The Ctrough for teicoplanin showed statistically significant relationships (P<0.05) with PLT, Scr, CLcr, eGFR, BUN and Cys-C. ROC curve analysis revealed that CLcr and eGFR were more sensitive and specific for Ctrough compared to the other factors. These findings should be considered in the clinical application of teicoplanin and for its dosage adjustment.

Antibiotic consumption in secondary and tertiary hospitals in Colombia: national surveillance from 2018-2020 / Consumo de antibióticos en hospitales de segundo y tercer nivel en Colombia: vigilancia nacional entre 2018 y 2020 / Consumo de antibióticos em hospitais secundários e terciários da Colômbia: vigilância nacional de 2018 a 2020

ABSTRACT Objective. To assess the compliance in secondary and tertiary level hospitals with monthly reporting of antibiotic consumption to the Colombian National Public Health Surveillance System (SIVIGILA-INS), and to describe reported antibiotic consumption during 2018-2020. Methods. This study involved a secondary analysis of antibiotic consumption data reported to SIVIGILA-INS. Frequency of hospital reporting was assessed and compared against expected reports, disaggregated by intensive care units (ICU)/non-ICU wards and geographical regions. Consumption was expressed as defined daily dose (DDD) per 100 occupied beds for seven antibiotics. Results. More than 70% of hospitals reported antibiotic consumption at least once in each of the three years (79% in ICU and 71% in non-ICU wards). Of these, ICU monthly reporting was complete (12 monthly reports per year) for 59% in the period 2018-2019 but only 4% in 2020. Non-ICU reporting was complete for 52% in 2019 and for 2% in 2020. Most regions had an overall decrease in reporting in 2020. Analysis of antibiotic consumption showed an increase for piperacillin/tazobactam, ertapenem, and cefepime from 2019 to 2020. Conclusions. There were gaps in the consistency and frequency of reporting. Efforts are needed to improve compliance with monthly reporting, which declined in 2020, possibly due to the COVID-19 pandemic. Non-compliance on reporting and data quality issues should be addressed with the hospitals to enable valid interpretation of antibiotic consumption trends.

RESUMEN Objetivo. Evaluar el cumplimiento de los hospitales de segundo y tercer nivel en la presentación mensual de información sobre el consumo de antibióticos en el Sistema Nacional de Vigilancia en Salud Pública de Colombia (SIVIGILA-INS) y describir el consumo de antibióticos reportado en el período 2018-2020. Métodos. Este estudio incluyó un análisis secundario de los datos del consumo de antibióticos reportado en SIVIGILA-INS. Se evaluó la frecuencia de los informes hospitalarios y se comparó con los informes esperados, desglosados por unidad de cuidados intensivos (UCI) y otros servicios distintos a la UCI, y por región geográfica. El consumo se expresó en dosis diaria definida (DDD) por 100 camas ocupadas para siete antibióticos. Resultados. Más del 70% de los hospitales notificaron el consumo de antibióticos al menos una vez en cada uno de los tres años (79% en la UCI y 71% en los servicios distintos a la UCI). De estos, el 59% de las UCI completaron los informes mensuales (12 informes en un año) entre el 2018 y el 2019, pero solo el 4% en el 2020. El 52% de los servicios distintos a la UCI completó los informes en el 2019 y el 2% en el 2020. En la mayoría de las regiones hubo una disminución general de la notificación en el 2020. El análisis del consumo de antibióticos mostró un aumento de piperacilina/tazobactam, ertapenem y cefepima del 2019 al 2020. Conclusiones. Se encontraron disparidades en la coherencia y en la frecuencia de la presentación de informes. Es necesario destinar esfuerzos para mejorar el cumplimiento de la notificación mensual, que disminuyó en el 2020 posiblemente debido a la pandemia de COVID-19. La falta de cumplimiento en la presentación de los reportes y los problemas de calidad de los datos deben abordarse con los hospitales para facilitar la interpretación válida de las tendencias de consumo de antibióticos.

RESUMO Objetivo. Avaliar o cumprimento da exigência de notificar mensalmente o consumo de antibióticos em hospitais secundários e terciários ao Sistema Nacional de Vigilância em Saúde Pública da Colômbia (SIVIGILA-INS) e descrever o consumo informado de antibióticos de 2018 a 2020. Métodos. Este estudo envolveu uma análise secundária dos dados de consumo de antibióticos enviados para o SIVIGILA-INS. A frequência de notificação pelos hospitais foi avaliada e comparada com a frequência esperada. Os dados foram desagregados entre unidades de terapia intensiva (UTIs) e enfermarias gerais e por regiões geográficas. O consumo foi expresso como dose diária definida (DDD) por 100 leitos ocupados para sete antibióticos. Resultados. Mais de 70% dos hospitais notificaram consumo de antibióticos pelo menos uma vez em cada um dos três anos (79% na UTI e 71% nas enfermarias gerais). Entre eles, 59% dos hospitais enviaram todas as notificações relativas a UTIs (12 notificações mensais) no período de 2018 a 2019, mas apenas 4% o fizeram em 2020. No caso das enfermarias gerais, 52% dos hospitais enviaram todas as notificações em 2019 e 2% o fizeram em 2020. A maioria das regiões teve uma diminuição geral no número de notificações enviadas em 2020. A análise do consumo de antibióticos revelou um aumento no uso de piperacilina/tazobactam, ertapeném e cefepima de 2019 para 2020. Conclusões. Houve lacunas na uniformidade e frequência das notificações. São necessários esforços para melhorar o cumprimento da exigência de notificações mensais, que, possivelmente devido à pandemia de COVID‑19, diminuiu em 2020. Problemas relacionados ao não cumprimento da exigência de notificação e à qualidade dos dados devem ser resolvidos junto aos hospitais para permitir uma interpretação válida das tendências de consumo de antibióticos.

Development of a LC-MS/MS method for the determination of vancomycin in human serum and validation of its clinical value / 中华检验医学杂志

Objective:The aim of our study is to develop an LC-MS/MS method using isotope internal standard for the determination of vancomycin in human blood serum and to validate its clinical value.Method:We conducted a methodological evaluation study using serum samples from 221 hospitalized patients (142 males and 79 females; mean age (59.31±15.32) years) who received treatments of vancomycin at the Sir Run Run Shaw Hospital of Zhejiang University between March 2021 and June 2022. In addition, thirty clinical residual serum samples from healthy individuals (15 males and 15 females; mean age (35.65±9.86) years) undergoing physical examination were used for methodological evaluation. The method was established using AB Sciex Triple Quad 4500 MD liquid chromatography-tandem mass spectrometer and chromatographic separation was carried out using a Phenyl-Hexyl column with gradient elution. The mobile phase was composed of 0.1% formic acid in water and methanol; the column temperature was 40℃; Vancomycin-[d12] TFA salt was used as the internal standard (IS). The sensitivity, specificity, linearity, accuracy, imprecision, matrix effect, and carry-over of the method were evaluated.Results:The detection limit of vancomycin was 0.2 mg/L and the lowest limit of quantification was 0.5 mg/L. It showed good linearity ( R2=0.998 4) in the 1 to 50 mg/L concentration range. Accuracy (recovery rate 87.45%-112.69%), intra-day and inter-day imprecision ( CV 4.91%-7.69%), internal standard standardized matrix factor (90.22%-104.29%). Carryover pollution was negligible. Of the 221 patients, the mean trough concentrations of vancomycin in serum was (13.15±8.56) mg/L. Conclusion:The LC-MS/MS method for the detection of serum vancomycin established in our laboratory meets the requirements of the reference method, and can be used for the monitoring of clinical therapeutic drugs.

Monitoring results and influencing factors of clozapine plasma concentration in patients with mental disorders / 中国医师杂志

Objective:To analyze the influencing factors of clozapine plasma concentration in patients with mental disorders after oral administration, so as to provide reference for individualized treatment.Methods:Retrospective analysis was made on 221 inpatient reports of Clozapine blood concentration monitoring in the Therapeutic Drug Monitoring Laboratory (TDM) of the Pharmacy Department of the Chaohu Hospital Affiliated to Anhui Medical University from January to October 2021, and information such as patient gender, age, body mass index (BMI), smoking history, clozapine dose, combined drug use and blood concentration monitoring results were collected; Single factor analysis of variance and binary logistic regression were used to analyze the monitoring results of clozapine blood concentration in patients with mental disorders and its influencing factors.Results:Among 221 monitoring reports, 74 cases (normal concentration group) had clozapine plasma concentration within the effective plasma concentration range (350-600 ng/ml), 103 cases (low concentration group) were lower than the effective plasma concentration range (<350 ng/ml), and 44 cases (high concentration group) were higher than the effective plasma concentration range (>600 ng/ml). The results of single factor analysis of variance showed that there were statistically significant differences in daily dose of clozapine, standard dose, smoking history, course of disease, and abnormal liver function of patients in different blood concentration groups of clozapine (all P<0.05). The most frequently used antipsychotic drugs in 221 patients with clozapine were sodium valproate, amisulpride, aripiprazole and lithium carbonate in turn. The proportion of clozapine combined with ≥2 antipsychotics in the normal concentration group was higher than that in the low concentration group and the high concentration group, and the difference was statistically significant ( P<0.05). The results of binary logistic regression analysis showed that the combination of one antipsychotic drug and ≥ two antipsychotic drugs might help the blood concentration of clozapine in patients with mental disorders reach the target concentration (350-600 ng/ml), and the combination of two drugs was more beneficial [ OR(95% CI): 1.795(0.753-4.282)], with a statistically significant difference ( P<0.05). Conclusions:Clozapine plasma concentration varies greatly among individuals, and the therapeutic window is narrow. It is necessary to adjust the dosage in combination with the basic information and clinical information of patients, and regularly monitor the plasma concentration, so as to achieve the safety and effectiveness of individualized drug use.

China Hospital Pharmacovigilance System-based study of trimetazidine-associated Parkinson's syndrome / 中国基层医药

Objective:To evaluate the active monitoring methods and population characteristics of trimetazidine-associated Parkinson's syndrome.Methods:The clinical data of patients with trimetazidine-associated Parkinson's syndrome who received treatment in Liaocheng People's Hospital from January 2019 to December 2020 were retrospectively analyzed using the China Hospital Pharmacovigilance System (CHPS).Results:In 4 883 patients included in the study,167 patients were alarmed by CHPS, of which 26 patients were confirmed positive by manual rechecks. The rate of positive pre-alarming by CHPS was 15.57%. The actual incidence of trimetazidine-associated Parkinson's syndrome was 0.53%. The average age of the 26 patients with Parkinson's syndrome was (75.08 ± 10.79) years. None of the 26 patients had a past history/family history of idiopathic Parkinson's disease. There were 21 patients (80.77%) aged over 65 years, 19 patients (73.08%) with a history of ischemic encephalopathy, 17 patients (65.38%) with positive symptoms in both limbs, 20 patients (76.92%) with abnormal brain CT or MRI findings, and 21 patients (80.77%) with medication doses of 60-70 mg/d. Among the 26 patients, 18 were female patients (69.23%) and 18 were patients with normal renal function (69.23%). The follow-up results showed that trimetazidine administration was not terminated in 14 patients (53.85%), symptoms were not alleviated or worsened in 8 patients (30.77%), and symptoms were alleviated or disappeared in 18 patients (69.23%).Conclusion:The use of CHPS can timely detect trimetazidine-associated Parkinson's syndrome. CHPS has significant advantages over traditional monitoring modes. Age > 65 years and a previous history of ischemic encephalopathy are risk factors for developing trimetazidine-associated Parkinson's syndrome. No history/family history of idiopathic Parkinson's disease, positive Alzheimer's disease symptoms in both limbs and abnormal brain CT and MRI findings contribute to early diagnosis and differentiation of trimetazidine- associated Parkinson's syndrome. Trimetazidine-associated Parkinson's syndrome is more common in women than in men. Trimetazidine-associated Parkinson's syndrome can also occur in a population with normal renal function or under a normal trimetazidine dose condition. Trimetazidine-associated Parkinson's syndrome is relatively rare. Patients with trimetazidine- associated Parkinson's syndrome have low awareness. Because of the difficult diagnosis and serious consequences, there is a need to strengthen research on trimetazidine-associated Parkinson's syndrome.

Advances in therapeutic drug monitoring of infliximab in patients with Crohn disease / 中国药房

Infliximab （IFX）， tumor necrosis factor-α inhibitor， is widely used in clinical practice for treating Crohn disease （CD）， but it is difficult to obtain the optimal therapeutic effect according to the conventional dose. It is recommended to perform therapeutic drug monitoring （TDM） for patients with poor therapeutic efficacy to guide clinical decisions. This paper reviews the pharmacokinetic characteristics of IFX， exposure-response relationship， the influencing factors of pharmacokinetic differences， and analytical methods in TDM. It is found that IFX doesn’t undergo liver or kidney metabolism， exhibits obvious exposure-response relationships in both the induction and maintenance phases of CD treatment； disease activity， albumin， antibodies to IFX （ATI） and other factors influence IFX’s exposure. It is recommended that trough concentration of IFX in the maintenance period should be kept above 3 μg/mL； the dose of IFX should be increased or medication interval should be shortened for patients with severe disease， low albumin levels and ATI formation， to promote therapeutic efficacy of IFX. It is suggested to use the same detection method for TDM of IFX in the same patient.

Influence of argumented renal clearance on teicoplannin serum concentrations in critical ill patients / 中国临床药理学与治疗学

AIM: By analyzing the teicoplannin serum concentration in patients with severe infection and comparing the monitoring results in patients with hyperrenal function and non-hyperrenal function, to provide reference for clinical rational drug use. METHODS: A retrospective analysis was conducted on 64 patients admitted to the department of critical care medicine of a tertiary level hospital from August 2019 to March 2021, and statistical analysis was performed on the monitoring results of teicoplannin, together with medication information and other biochemical indicators of these patients. RESULTS: Sixty-four patients had total 110 times of drug monitoring. 32.7% of ICU patients had renal hyperfunction, and the average serum concentration was 13.6 mg/L. Nearly half of blood concentrations of the monitored patients could not reach the therapeutic target of teicoplanin. For patients without argumented real clearance, increasing the maintenance dose of teicoplanin can significantly increase the blood concentration. While for those with argumented real clearance, the blood concentration of teicoplanin had no significant difference in different maintenance dose groups. Further correlation study found that the serum concentration of teicoplanin in patients with argumented real clearance was significantly positively correlated to cystatin C level, and significantly negatively correlated to albumin level. CONCLUSION: The incidence of renal hyperfunction in ICU patients is high, and the maintenance dose of teicoplanin 600 mg may not be effective for severe infection. To improve the effect of teicoplanin in severe patients, the drug concentration should be monitored to adjust the dose.

Research progress in plasma concentration monitoring of rivaroxaban / 中国临床药理学与治疗学

Rivaroxaban, a novel oral anticoagulant drug, is widely prescribed in clinical practice. Rivaroxaban offers predictable pharmacokinetic and pharmacodynamic properties, a lowprobability of drug-drug and food-drug interactions. Compared with warfarin, rivaroxaban does not require continuous therapeutic monitoring and can be administered in fixed doses.However,in certain emergency clinical situations, such as bleeding, acute stroke, acute kidney injury, prior to urgent surgery and in the suspected accumulation of durg, plasma concentration monitoring of rivaroxaban is necessary and important for patients. Existing studies proved that there were significant individual variability and wide range in the plasma rivaroxaban concentration, which increased the risk of clinical use. Therefore, Data in the degree of rivaroxaban concentration may provide recommendations for the clinical application to promote medication safety and individuality in the future. This article collected the latest literatures and case reports related to research progress of rivaroxaban plasma concentration monitoring, and Summarized influencing factors, monitoring methods, so as to provide a basis for further study on rational use of rivaroxaban in clinical.

Effect of augmented renal clearance (ARC) on the pharmacokinetics, efficacy, and safety of vancomycin in patients with infective endocarditis / 中国临床药理学与治疗学

AIM: To study the effects of augmented renal clearance (ARC) on vancomycin pharmacokinetics, efficacy, and safety in patients with infective endocarditis, so as to provide better guidance for vancomycin medication. METHODS: The retrospective analysis was conducted. Patients data from the hospital medical record system from April 2020 to April 2023 during the cardiovascular surgery with use of vancomycin were collected. The subjects were divided into normal group and ARC group according to glomerular filtration rate (eGFR). According to the population pharmacokinetic model, the measured trough concentration was used for a Bayesian approach to estimate individual pharmacokinetic parameters and analyze influence of ARC on vancomycin pharmacokinetics. RESULTS: A total of 163 patients were included in this study. The incidence of ARC was 23.31%. The age of patients in ARC group was significantly lower than that in normal group (P<0.05). Moreover, the steady-state trough concentration (Cmin), trough concentration compliance rate, area under the curve (AUC), and elimination half life (t1/2) were significantly lower in ARC group than that in normal group (P<0.05). In addition, ARC group had significantly higher clearance (CL) and elimination rate than normal group (P<0.05). Correlation analysis showed that Cmin was positively correlated with AUC (r

Pharmaceutical care for a Crohn's disease patient with hypoalbuminemia and non-response to infliximab / 药学实践杂志

Objective To investigate the role of clinical pharmacists in individualized treatment and pharmaceutical care for a Crohn’s disease patient with non-response to infliximab. Methods The clinical pharmacist participated in the pharmaceutical care for a Crohn’s disease patient with hypoalbuminemia. Clinical pharmacists interpreted the blood concentration results of infliximab based on literature review, analyzed the pharmacokinetic process of drugs, and suggested that low serum albumin levels may cause the accelerated drug elimination and resulted in reduced drug concentration and secondary non-response. Results Clinical pharmacists assisted clinician adjusting the medication regimen and the patient recovered well after the new treatment plan. Conclusion With good understanding in medication pharmacokinetics and the blood test results, clinical pharmacists can help to solve the drug therapy related problems and establish an individual treatment plan to improve the safety and effectiveness of the biological medications.

Application of machine learning in the therapeutic drug monitoring and individual drug therapy / 中国药房

Machine learning has been applied in the medical field due to its powerful data analysis and exploration capabilities. In recent years， more and more studies have applied it to therapeutic drug monitoring and individual drug therapy of immunosuppressants， anti-infective drugs， antiepileptic drugs， etc. Compared with the traditional population pharmacokinetic modeling methods， the constructed models based on machine learning can predict blood drug concentration and drug dose more accurately， improve the level of clinical precision drug use and reduce the occurrence of adverse drug reactions. Based on this， this article reviews the application of machine learning in therapeutic drug monitoring and individual drug therapy， with a view to providing theoretical basis and technical support for clinical precise drug use.

Research progress in pharmacokinetics/pharmacodynamics and drug use of meropenem in special population / 中国药房

Meropenem is the first choice for the treatment of multi-drug-resistant bacterial infections， which has been widely used in clinical practice. However， the physiological and pathological characteristics of special populations have a significant impact on the pharmacokinetics/pharmacodynamics （PK/PD） parameters of meropenem， so it is necessary to develop individualized drug administration plan according to the characteristics of patients in clinical application. Therefore， this paper summarizes PK/PD characteristics and application of meropenem in special population， and recommends the dosage of meropenem as follows： 10-40 mg/kg， q8 h for children； 1 g， q8-12 h for elderly patients； 0.75 g， q8 h for the patients with renal insufficiency who received continuous veno-venous hemofiltration and continuous veno-venous hemodialysis； 1 g， q8 h prolonged infusion until 3 hours or 2 g， q8 h for patients with hyperrenal function； 1 g， q8 h after 2 g loading dose for patients with cirrhosis.

Effects of individualized dosing regimen on blood trough concentration of vancomycin and renal function in critically ill patients / 中国药房

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.