Chinese consensus guidelines for therapeutic drug monitoring of polymyxin B, endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.

Modifications to a Drug Ordering System Improved the Implementation Rate of Therapeutic Drug Monitoring for Voriconazole / 医薬品情報学

Introduction: Voriconazole (VRCZ) is a triazole antifungal agent for which therapeutic drug monitoring (TDM) is recommended. At Juntendo University Hospital, the VRCZ TDM implementation rate was 42% between January 2011 and October 2017. Here, we report that modifications to the hospital’s drug ordering system improved the implementation rate of VRCZ TDM.Method: In August 2018, the drug ordering system was modified so that a message appeared on the screen to notify clinicians of the need to monitor VRCZ blood concentrations and to recommend a date for sample collection. In addition, the laboratory orders for VRCZ levels were digitized. We compared two one-year periods before and after implementation of the modifications (August 2017 to July 2018 and August 2018 to July 2019) to verify the effect of the changes.Result: Results showed an increase in the TDM implementation rate: 12 patients (42.8%) received TDM before modification of the system, and 26 patients (92.9%) received TDM after modification of the system. Further, the rate of blood sampling at the recommended time point for estimating blood concentration (day 5-7 after the start of administration) improved after system modification, i.e., blood samples were collected from 18 patients (64.3%) at the steady state point. In contrast, blood samples were collected from only 6 patients (21.4%) before system modification. When blood concentrations deviated from the target range in patients who received TDM, clinicians took appropriate actions, such as reducing drug doses, prescribing drug holidays, or discontinuing medications.Conclusion: A system that provides information related to VRCZ blood concentration measurements can help clinicians provide patients with optimal pharmacotherapy.

Modern Methods for Analysis of Antiepileptic Drugs in the Biological Fluids for Pharmacokinetics, Bioequivalence and Therapeutic Drug Monitoring

Epilepsy is a chronic disease occurring in approximately 1.0% of the world's population. About 30% of the epileptic patients treated with availably antiepileptic drugs (AEDs) continue to have seizures and are considered therapy-resistant or refractory patients. The ultimate goal for the use of AEDs is complete cessation of seizures without side effects. Because of a narrow therapeutic index of AEDs, a complete understanding of its clinical pharmacokinetics is essential for understanding of the pharmacodynamics of these drugs. These drug concentrations in biological fluids serve as surrogate markers and can be used to guide or target drug dosing. Because early studies demonstrated clinical and/or electroencephalographic correlations with serum concentrations of several AEDs, It has been almost 50 years since clinicians started using plasma concentrations of AEDs to optimize pharmacotherapy in patients with epilepsy. Therefore, validated analytical method for concentrations of AEDs in biological fluids is a necessity in order to explore pharmacokinetics, bioequivalence and TDM in various clinical situations. There are hundreds of published articles on the analysis of specific AEDs by a wide variety of analytical methods in biological samples have appears over the past decade. This review intends to provide an updated, concise overview on the modern method development for monitoring AEDs for pharmacokinetic studies, bioequivalence and therapeutic drug monitoring.

Evaluation of Viva-E Drug Testing System / 대한진단검사의학회지

BACKGROUND: The importance and usefulness of therapeutic drug monitoring (TDM) have been emphasized, and analysis of drugs has been increased in clinical laboratories. We evaluated the analytical performance and clinical usefulness of a recently introduced enzyme multiplied immunoassay instrument, Viva-E Drug Testing System (Dade Behring Inc., USA). METHODS: Using patients' samples and quality control material, we evaluated the analytical performance of Viva-E for a total of 11 drugs (cyclosporine, tacrolimus, mycophenolic acid, valproic acid, digoxin, theophylline, carbamazepine, phenytoin, phenobarbital, vancomycin, and gentamicin) with respect to linearity, precision, and correlations with other methods according to CLSI guidelines. Cobas Integra 800 (Roche Diagnostics, Switzerland) and API 4000 LC-MS/MS System (Applied Biosystems, USA) were used to make a comparison. In addition, we analyzed analysis time. RESULTS: Viva-E showed a good linearity (r2 > or = 0.97) for all items. Within-run CVs were within 5% and total CVs were within 10% for all drugs except for tacrolimus and digoxin at low concentrations. The system correlated well with the other methods (r=0.9283-0.9778). The time required for reporting the first sample was 11 min and the analysis time was 1.1 min. CONCLUSIONS: Since Viva-E showed a good analytical performance required for TDM in its linearity, precision, and accuracy with its wide drug menus including cyclosporine, tacrolimus, and mycophenolic acid, stat and random accessing functions, and the consolidation to a single workstation, it could be very useful in the clinical laboratory for various needs.

Analysis of Monitoring Results on Cyclosporin A Plasma Concentration in Bone Marrow Transplantation Recipients / 中国药房

OBJECTIVE:To observe the efficacy and safety of the effective blood concentration of cyclosporin A in patients after bone marrow transplantation.METHODS:By fluorescence polarization immunoassay(FPIA),the whole blood trough concentration of CsA in 14 patients after undergoing bone marrow transplantation was monitored for 216 times in total from day 1 to day 466,and the monitoring results were analyzed.RESULTS:The effective blood concentrations of CsA in patients with chronic myelocytic leukemia(CML),acute non lymphocytic leukemia(AML),acute lymphoblastic leukemia (ALL),Mediterranean disease(THAL),and pancytopenia were(50～450) ng?mL~(-1),(100～450) ng?mL~(-1),(100～350) ng?mL~(-1)(200～500) ng?mL~(-1),and(250～500) ng?mL~(-1),respectively.Rejection reaction appeared in 7 cases after bone marrow transplantation,with whole blood trough concentration of CsA ranged from 67.4 ng?mL~(-1) to 189.34 ng?mL_(-1) (125.44?39.56 ng?mL~(-1)on average).Adverse drug reaction appeared in 3 cases,with trough concentration of CsA ranged from 412.5 ng?mL~(-1) to 548.62 ng?mL~(-1)(481.39?68.08 ng?mL~(-1) on average).CONCLUSION:Timely monitoring of plasma concentration of CsA and modifying of the dosage regimen can avoid the occurrence of rejection reaction and adverse drug reaction,which is of great significance for patients' medication safety and efficacy.

Therapeutic Drug Monitoring(TDM) of Psychotropic Drugs

Clinicians can use therapeutic drug monitoring(TDM) to optimise dosage decisions with psychotropic drugs, in order to maximize efficacy and prevent toxicity, especially when individuals are nonresponsive to treatment or vulnerable to adverse reactions with standard doses because age, disease states or drug interactions. Currently therapeutic drug concentrations have been established for the TCA and lithium. There is also evidence for the usefulness of TDM with carbamazepine, valproic acid and some antipsychotic drugs. However for most psychotropic drugs this approach remains experimental. TDM-assisted psychiatric treatment is potentially useful and cost effective, particularly when applied by psychiatrists who are knowledgeable of pharmacokinetics and pharmacodynamics.