Evaluation of Omeprazole Limited Sampling Strategies to Estimate Constitutive Cytochrome P450 2C19 Activity in Healthy Adults: Erratum
No abstract available (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Erratum Source Type: research

An Investigation into Variability in the Therapeutic Response to Deferiprone in Patients with Thalassemia Major: Retraction
No abstract available (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Erratum Source Type: research

Different Underlying Mechanism Might Explain the Absence of a Significant Difference in Area Under the Concentration–Time Curve of Linezolid for Different ABCB1 Genotypes
No abstract available (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Letters to the Editor Source Type: research

Therapeutic Drug Monitoring of Second-Generation Antipsychotics for the Estimation of Early Drug Effect in First-Episode Psychosis
No abstract available (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Letters to the Editor Source Type: research

The Smell of Death: An Unusual Case of Poisoning With the Organophosphorus Pesticide Chlorfenvinphos
No abstract available (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Letters to the Editor Source Type: research

Stability of Antidepressants and Antipsychotics in Gel Separator Tubes
No abstract available (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Letters to the Editor Source Type: research

Targeted Proteomic Analysis Detects Acute T Cell–Mediated Kidney Allograft Rejection in Belatacept-Treated Patients
Background: There is an unmet need for reliable minimally invasive diagnostic biomarkers for immunological allograft monitoring and for the detection of acute kidney transplant rejection. Here, targeted proteomic analysis was applied to compare 92 proteins in sera of belatacept-treated patients who had biopsy-proven, acute T-cell–mediated rejection (aTCMR) with patients without aTCMR. Methods: Proximity extension immunoassay was used to measure 92 inflammation-related protein concentrations in the prerejection and rejection sera of 11 patients with aTCMR and 9 patients without aTCMR. This assay uses 2 matched ol...
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Absence of Relationship Between Crohn's Disease Activity Index or C-Reactive Protein and Infliximab Exposure Calls for Objective Crohn's Disease Activity Measures for the Evaluation of Treatment Effects at Treatment Failure
Conclusions: No significant relationship between disease activity, as evaluated by CDAI or CRP, and IFX exposure was identified. AUC did not add benefit compared with Cmin. These findings support the continued use of Cmin and call for stringent objective disease activity (bio-)markers (eg, endoscopy) to form the basis of personalized IFX therapy for Crohn's disease patients with IFX treatment failure. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Biomarkers of Drug-Induced Liver Toxicity
Abstract: Drug-induced liver injury (DILI) is a comprehensive phenomenon. The injury to the liver may occur as an unexpected and undesired reaction to a therapeutic dose of a drug (idiosyncratic reaction) or as an expected therapeutic effect of the direct (intrinsic) toxicity of a drug taken in a large enough dose to cause liver injury. The direct toxicity (type A) reactions represent an extension of the drug's therapeutic effect; they occur relatively frequently and are typically dose-related and frequency-of-exposure-related. By contrast, idiosyncratic reactions, or type B reactions, are unpredictable, occurring only i...
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Review Articles: Focus on Pharmacodynamic Drug Monitoring Source Type: research

Biomarkers of Drug-Induced Kidney Toxicity
Abstract: Blood urea nitrogen and serum creatinine are imperfect markers of kidney function because they are influenced by many renal and nonrenal factors independent of kidney function. A biomarker that is released directly into the blood or urine by the kidney in response to injury may be a better early marker of drug-induced kidney toxicity than blood urea nitrogen and serum creatinine. Urine albumin and urine protein, as well as urinary markers kidney injury molecule-1 (KIM-1), β2-microglobulin (B2M), cystatin C, clusterin, and trefoil factor-3 (TFF-3) have been accepted by the Food and Drug Administration and E...
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Review Articles: Focus on Pharmacodynamic Drug Monitoring Source Type: research

Strategies for Individualized Dosing of Clotting Factor Concentrates and Desmopressin in Hemophilia A and B
In this study, a review of the existing literature on the individualization of dosing based on PK guidance was performed. In total, 79 articles were included. The methods to individualize dosing were divided into 3 categories: (1) methods using clinical parameters, (2) empirical individual PK-guided methods, and (3) maximum a posteriori (MAP) Bayesian estimation methods. The clinical parameter mainly used to individualize dosing is bleeding phenotype. Dosing based on bleeding phenotype may decrease clotting factor consumption. However, with this method, it is not possible to individualize on-demand dosing during bleeding e...
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Review Articles: Focus on Pharmacodynamic Drug Monitoring Source Type: research

Pharmacokinetic and Pharmacodynamic Drug Monitoring of Direct-Acting Oral Anticoagulants: Where Do We Stand?
Abstract: For decades, oral anticoagulation has been based on vitamin K antagonist such as warfarin, which requires pharmacodynamic (PD) drug monitoring to guide the therapy. The drug effect is measured by the clotting test prothrombin time and expressed as international normalized ratio. New direct oral anticoagulants are increasingly used in fixed-dose regimens but are licensed without any therapy monitoring. However, extensive clinical experiences have demonstrated that interindividual variations in the response to the therapy with direct oral anticoagulants do exist. In situations such as bleeding or thrombosis, ther...
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Review Articles: Focus on Pharmacodynamic Drug Monitoring Source Type: research

Concentration–Effect Relationships of Psychoactive Drugs and the Problem to Calculate Therapeutic Reference Ranges
Conclusions: This review provides a discussion on why simple correlation analyses of psychoactive drug concentrations in blood and clinical effects are obsolete for flexible-dose studies or TDM databases. TDM databases, however, can and should be used to calculate drug concentrations in blood of patients who had responded to the drugs. Interquartile ranges can be regarded and used as preliminary therapeutic reference ranges. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Review Articles: Focus on Pharmacodynamic Drug Monitoring Source Type: research

Pharmacodynamic Monitoring of Antiepileptic Drug Therapy
Abstract: Epilepsy is characterized by seizures recurring at interindividually differing time intervals. It may be difficult to assess drug response if time intervals between seizures are long. Thus, the existence of surrogate parameters that could be used to reliably identify drug efficacy and tolerability at an early stage and also as prognostic factors would be desirable. Electroencephalography, magnetic resonance imaging, and genetic markers are the domains to be assessed in this respect. The availability of clinically useful pharmacodynamic parameters is, however, currently disappointing. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Review Articles: Focus on Pharmacodynamic Drug Monitoring Source Type: research

Pharmacodynamic Monitoring of mTOR Inhibitors
Abstract: Pharmacodynamic (PD) monitoring may complement routine pharmacokinetic monitoring of mTOR inhibitors (mTORis) in an attempt to better guide individualized sirolimus (SRL) or everolimus (EVR) treatment after organ transplantation. This review focuses on current knowledge about PD biomarkers for personalized mTORi therapies. Different strategies have already been used in the evaluation of the pharmacodynamics of SRL and EVR as a proxy for their effects on the immune response after transplantation. These include measuring p70S6K (70 kDa ribosomal protein S6 kinase) activity, p70S6K phosphorylation (P-p70S6K), or P...
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Review Articles: Focus on Pharmacodynamic Drug Monitoring Source Type: research

Pharmacodynamic Therapeutic Drug Monitoring for Cancer: Challenges, Advances, and Future Opportunities
Abstract: In the modern era of cancer treatment, with targeted agents superseding more traditional cytotoxic chemotherapeutics, it is becoming increasingly important to use stratified medicine approaches to ensure that patients receive the most appropriate drugs and treatment schedules. In this context, there is significant potential for the use of pharmacodynamic biomarkers to provide pharmacological information, which could be used in a therapeutic drug monitoring setting. This review focuses on discussing some of the challenges faced to date in translating preclinical pharmacodynamic biomarker approaches to a clinical...
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Review Articles: Focus on Pharmacodynamic Drug Monitoring Source Type: research

Pharmacodynamic Monitoring of Biological Therapies in Chronic Inflammatory Diseases
Conclusions: The primary goal of pharmacodynamic monitoring is to optimize the response, but it can also have an impact on safety, costs, patient adherence, etc. Ideally, the constant remote monitoring of patient-reported disease activity is expected to become the standard, facilitated by mHealth technologies. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Review Articles: Focus on Pharmacodynamic Drug Monitoring Source Type: research

Pharmacogenetics Biomarkers Predictive of Drug Pharmacodynamics as an Additional Tool to Therapeutic Drug Monitoring
Abstract: Conventional therapeutic drug monitoring refers to the individualization of drug dosage by maintaining plasma or blood drug concentrations within a targeted therapeutic range. Accordingly, an individualized dose is proposed to the clinician according to the drug plasma or blood concentration using an a posteriori approach. Pharmacogenetics (PGx) has recently emerged as an additional tool to refine dose selection or, more interestingly to select, a priori, the first dose to administer. To date, the vast majority of genes explored in the context of PGx are those coding for metabolizing enzymes or membrane drug tr...
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Review Articles: Focus on Pharmacodynamic Drug Monitoring Source Type: research

Circulating Cell-Free DNA—Diagnostic and Prognostic Applications in Personalized Cancer Therapy
Abstract: Genomic analyses in oncologic care allow for the development of more precise clinical laboratory tests that will be critical for personalized pharmacotherapy. Traditional biopsy-based approaches are limited by the availability of sequential tissue specimens to detect resistance. Blood-based genomic profiling (“liquid biopsy”) is useful for longitudinal monitoring of tumor genomes and can complement biopsies. Tumor-associated mutations can be identified in cell-free tumor DNA (ctDNA) from patient blood samples and used for monitoring disease activity. The US Food and Drug Administration approved a li...
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Review Articles: Focus on Pharmacodynamic Drug Monitoring Source Type: research

Improving Therapeutic Decisions: Pharmacodynamic Monitoring as an Integral Part of Therapeutic Drug Monitoring
Abstract: Although the monitoring of drug therapies based on the determination of drug concentrations in biological materials is certainly an important instrument for individualized dosing and dose adjustment with a broad variety of pharmaceuticals, its role is limited by the fact that it does not reflect pharmacodynamic (PD) and toxicodynamic interactions such as those caused by individual and environment-related factors. However, these interactions are important for both the efficacy and the safety of the drug therapy. Therefore, during recent years, there is an increased interest in personalized drug therapy as reflec...
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Editorial Source Type: research

Ganciclovir Therapeutic Drug Monitoring: A Case Series
This article presents 3 cases of immunocompromised patients for whom therapeutic drug monitoring of ganciclovir in combination with cytomegalovirus viral load measurement was used to guide treatment. The first patient is diagnosed with thymoma A, the second is a heart transplant recipient, and the third is an HIV-positive patient. These patients were all diagnosed with cytomegalovirus and treated with ganciclovir. Our case studies illustrate how therapeutic drug monitoring–guided dosing can be helpful in the management of these complex cases. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - March 19, 2019 Category: Drugs & Pharmacology Tags: Grand Rounds Source Type: research

Simultaneous Quantification of Nine Antimicrobials by LC-MS/MS for Therapeutic Drug Monitoring in Critically Ill Patients
Background: Adequate antibiotic treatment is a prerequisite for the successful treatment of systemic infections. Based on accumulating scientific evidence, a fixed dosage regimen can lead to insufficient and ineffective antibiotic therapy. Thus, the aim of this study was to develop and validate a simplified, but sensitive method for the simultaneous quantification of antimicrobials by using liquid chromatography with tandem mass spectrometry (LC-MS/MS) for the development of personalized therapy regimens using therapeutic drug monitoring. Methods: A method was developed for the simultaneous quantification of 9 antimic...
Source: Therapeutic Drug Monitoring - February 1, 2019 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Pharmacokinetic Characteristics and Limited Sampling Strategies for Therapeutic Drug Monitoring of Colistin in Patients With Multidrug-Resistant Gram-Negative Bacterial Infections
Conclusions: Our study clarifies the PK characteristics of successful colistin treatment using TDM. Further evaluations in a larger patient population are needed to confirm the clinical usefulness of colistin TDM. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 14, 2019 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Switching Immunosuppression From Cyclosporine to Tacrolimus in Kidney Transplant Recipients Based on CYP3A5 Genotyping
Conclusions: Our preliminary study supports the use of CYP3A5 genotyping to guide the initial dosing of Tac when converting the immunosuppression therapy from CsA to Tac. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 14, 2019 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Catalase C-262T Polymorphism Is a Risk Factor for Valproic Acid–Induced Abnormal Liver Function in Chinese Patients With Epilepsy
This study aimed to investigate the relationships between GST mu 1 (GSTM1), GST theta 1 (GSTT1), CAT C-262T, GPx1 Pro200Leu, and SOD2 Val16Ala polymorphisms and the risk of abnormal liver function in Chinese epileptic patients treated with VPA monotherapy. Methods: According to the levels of liver function indicators, a total of 267 epileptic patients between 1 and 65 years of age were divided into normal liver function group and abnormal liver function group. GSTM1 and GSTT1 polymorphisms were determined using polymerase chain reaction (PCR) amplification based on the absence of a PCR amplification product. CAT, GPx1, ...
Source: Therapeutic Drug Monitoring - January 14, 2019 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Relationship Between UGT1A4 and UGT2B7 Polymorphisms and the Steady-State Plasma Concentrations of Lamotrigine in Patients With Treatment-Resistant Depressive Disorder Receiving Lamotrigine as Augmentation Therapy
Conclusions: This study suggests that these genetic polymorphisms do not affect the Css of lamotrigine in patients with treatment-resistant depressive disorder receiving lamotrigine as augmentation therapy. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 14, 2019 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Quantification of Thiopurine Nucleotides in Erythrocytes and Clinical Application to Pediatric Acute Lymphoblastic Leukemia
Conclusions: In this study, an assay for the quantification of 6TG and 6MMP in RBCs was established and applied to pediatric ALL patients. Interindividual variability in 6MP metabolite concentrations was considerable and associated with elevation of liver enzymes, which may be useful in the clinical monitoring of 6MP maintenance therapy in pediatric ALL patients. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 14, 2019 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Estimation of Unbound Carboplatin Clearance From Total Plasma Concentrations as a Means of Facilitating Therapeutic Drug Monitoring
Conclusions: The linear equation gives a relatively good estimation of CLU based on P concentrations, making PK-based carboplatin dose adaptation possible for centers without ultrafiltration facilities. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 14, 2019 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Darunavir Population Pharmacokinetic Model Based on HIV Outpatient Data
Background: Darunavir is a second-generation protease inhibitor and is registered for the treatment of HIV-1 infection. The aim of this study was to develop and validate a darunavir population pharmacokinetic model based on data from daily practice. Methods: Data sets were obtained from 2 hospitals: ASST Fatebenefratelli Sacco University Hospital, Italy (hospital A), and University Medical Center Groningen, the Netherlands (hospital B). A pharmacokinetic model was developed using data from the largest data set using the iterative two-stage Bayesian procedure within the MWPharm software package. External validation was...
Source: Therapeutic Drug Monitoring - January 14, 2019 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Pharmacokinetics of Daclatasvir, Sofosbuvir, and GS-331007 in a Prospective Cohort of Hepatitis C Virus–Positive Kidney Transplant Recipients
In this study, plasma samples of 16 HCV-positive kidney transplant recipients receiving daclatasvir and sofosbuvir were collected at 4 time points at days 1, 7, 14, 21, 56, and 84 after start of treatment. Inclusion criteria were stable graft function and an estimated glomerular filtration rate (eGFR)>30 mL/min/1.73 m2. Daclatasvir, sofosbuvir, and GS-331007 (inactive metabolite of sofosbuvir) plasma concentrations were determined using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Results: All patients showed a rapid virological response with HCV RNA below the detection limit 2...
Source: Therapeutic Drug Monitoring - January 14, 2019 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Impact of Disease on Amikacin Pharmacokinetics and Dosing in Children
Conclusions: Disease condition was significant in influencing amikacin PK in children. To reach the same target concentrations (64 mg/L peak concentration) with a daily-dose plan, burn patients need higher doses than cancer patients. Future investigations are needed to explore the impact of other diseases on amikacin disposition in children, and to prospectively validate the proposed dosing strategy. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 14, 2019 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Low Serum Trough Concentrations and High Vancomycin Minimum Inhibitory Concentration in Methicillin-Sensitive Staphylococcus aureus From Hemodialysis Patients in Brazil
Conclusions: The therapeutic range of vancomycin was not achieved, and vancomycin MIC was surprisingly high in methicillin-sensitive S. aureus. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 14, 2019 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Simultaneous Quantification of Nine Antimicrobials by LC-MS/MS for Therapeutic Drug Monitoring in Critically Ill Patients
Background: Adequate antibiotic treatment is a prerequisite for the successful treatment of systemic infections. Based on accumulating scientific evidence, a fixed dosage regimen can lead to insufficient and ineffective antibiotic therapy. Thus, the aim of this study was to develop and validate a simplified, but sensitive method for the simultaneous quantification of antimicrobials by using liquid chromatography with tandem mass spectrometry (LC-MS/MS) for the development of personalized therapy regimens using therapeutic drug monitoring. Methods: A method was developed for the simultaneous quantification of 9 antimic...
Source: Therapeutic Drug Monitoring - January 14, 2019 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

A Method for Direct Monitoring of Atorvastatin Adherence in Cardiovascular Disease Prevention: Quantification of the Total Exposure to Parent Drug and Major Metabolites Using 2-Channel Chromatography and Tandem Mass Spectrometry
Conclusions A fast and reliable assay for the quantification of atorvastatin and its 5 major metabolites in clinical blood samples is reported. Limitations of preanalytical stability were solved using the sum of the acid and lactone forms. The assay is feasible for implementation in clinical practice, and the sum of parent drug and metabolites may be used for direct monitoring of atorvastatin adherence. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 14, 2019 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

A Fully Automated Method for the Determination of Serum Belatacept and Its Application in a Pharmacokinetic Investigation in Renal Transplant Recipients
Conclusions: We have developed an automated, accurate, and precise assay for the determination of belatacept serum concentrations. The assay was successfully applied in a pharmacokinetic study in renal transplant recipients receiving belatacept infusions. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 14, 2019 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

New Mass Spectrometric Approaches for the Quantitative Evaluation of Anticancer Drug Levels in Treated Patients
Abstract: Alternatively to the well-consolidated liquid chromatography coupled to tandem mass spectrometry approach used for the evaluation of anticancer drug concentrations in treated patients, new mass spectrometric methods have been proposed and tested recently. They exhibited faster analysis time and, at first sight, simpler instrumental approaches. However, results obtained by these methods require an in-depth evaluation, because of their strong dependence on the experimental set-up. In this short review, the quantification of irinotecan, sunitinib, and 6-α-hydroxy paclitaxel (the main metabolite of paclitaxel...
Source: Therapeutic Drug Monitoring - January 14, 2019 Category: Drugs & Pharmacology Tags: Review Article Source Type: research

Rebuttal Letter to the Editor Kloosterboer et al., Ther Drug Monit 2018;40: 344–350
No abstract available (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - November 16, 2018 Category: Drugs & Pharmacology Tags: Letters to the Editor Source Type: research

Critical Remarks to Kloosterboer et al. June 2018
No abstract available (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - November 16, 2018 Category: Drugs & Pharmacology Tags: Letters to the Editor Source Type: research

Documentation of a Little-Studied Designer Benzodiazepine After a Controlled Single Administration: II. Concentration Profile of Deschloroetizolam in Saliva
No abstract available (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - November 16, 2018 Category: Drugs & Pharmacology Tags: Letters to the Editor Source Type: research

Evaluation of Omeprazole Limited Sampling Strategies to Estimate Constitutive Cytochrome P450 2C19 Activity in Healthy Adults
Conclusions: Omeprazole LSS performed poorly in estimating CL/F using 2 separate estimation approaches and does not seem to be a suitable method for determining CYP2C19 activity. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - November 16, 2018 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Evaluation of Infliximab and Anti-infliximab LISA-TRACKER Immunoassays for the Therapeutic Drug Monitoring of SB2 Infliximab Biosimilar
Conclusions: LISA-TRACKER IFX and anti-IFX assays are suitable for the monitoring of patients treated with SB2. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - November 16, 2018 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Addressing the Fentanyl Analogue Epidemic by Multiplex UHPLC-MS/MS Analysis of Whole Blood
Conclusions: A selective, highly sensitive, and robust method for determination of a large panel of fentanyls and naloxone in blood was developed and validated. Naloxone was included to monitor use and efficacy of the opioid antidote in cases of fentanyl overdoses. The method demonstrated good ability to separate structural isomers, which is important to differentiate between the numerous available fentanyls with variable potency, toxicity, and legal status. The developed method can be used to identify fentanyls on the drug market to help combat the fentanyl crisis. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - November 16, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

A Population Pharmacokinetic–Pharmacogenetic Model of Lamotrigine in Chinese Children With Epilepsy
Conclusions: A PPK–pharmacogenetic model of LTG in Chinese children with epilepsy was successfully established with nonlinear mixed effects modeling. Genotyping for UGT2B7-161C>T may be useful in titrating the optimal LTG dose. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - November 16, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Influence of Inflammation on the Pharmacokinetics of Perampanel
Conclusions: Irrespective of concomitant administration of enzyme-inducing AEDs, the serum perampanel concentration showed a marked increase in patients with inflammation. However, this increase was not associated with central nervous system toxicity. Although it is unknown whether the concentration of free and/or bound perampanel was increased, it seems likely that dose reduction is unnecessary for elevation of the serum perampanel level in patients with inflammation. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - November 16, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

An LC-MS/MS Method for Absolute Quantification of Nivolumab in Human Plasma: Application to Clinical Therapeutic Drug Monitoring
Conclusions: An absolute quantification method for nivolumab using LC-MS/MS was successfully developed and validated. Combined with PPK analysis, this method should be useful for the therapeutic drug monitoring of nivolumab in clinical practice. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - November 16, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Discrimination of Anti-drug Antibodies With Neutralizing Capacity in Infliximab- and Adalimumab-Treated Patients: Comparison of the Homogeneous Mobility Shift Assay and the Affinity Capture and Elution Assay
Conclusions: Results obtained after HMSA and ACE analysis are strongly correlated, and in both assays, high ADA levels are a specific marker of neutralizing capacity. The detection of multimeric complexes by HMSA also selectively identifies sera with neutralizing capacity. These data support the use of these assays as quantitative rather than simple qualitative measures of ADA. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - November 16, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Effects of Proton Pump Inhibitor Coadministration on the Plasma Concentration of Erlotinib in Patients With Non–Small Cell Lung Cancer
Background: Erlotinib is used for treating non–small cell lung cancer (NSCLC). Intestinal absorption of erlotinib is impaired under gastric pH elevation; therefore, coadministration of gastric acid suppressants may provide lower blood concentration of erlotinib. We investigated the effects of erlotinib coadministration with proton pump inhibitors (PPIs) and histamine H2 receptor blockers (H2RBs) on the plasma concentration of erlotinib and erlotinib-induced adverse reaction in patients with NSCLC. Methods: Forty-two patients receiving erlotinib therapy for NSCLC were recruited for this study. Association of adve...
Source: Therapeutic Drug Monitoring - November 16, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Validation of a Nomogram for Achieving Target Trough Concentration of Vancomycin: Accuracy in Patients With Augmented Renal Function
Background: Adjustment of initial vancomycin (VCM) dosage has been recommended on the basis of the renal function nomogram in therapeutic drug monitoring guidelines in Japan. However, this nomogram has not been clinically validated, and few studies have focused on its usefulness in patients with risk of augmented renal function. Therefore, this study aimed to evaluate the validity of the VCM nomogram and the association between patient conditions related to augmented renal function and its accuracy. Methods: In this retrospective study, we screened data of 398 patients who received VCM and had estimated glomerular fil...
Source: Therapeutic Drug Monitoring - November 16, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Simultaneous Determination of Cefalexin, Cefazolin, Flucloxacillin, and Probenecid by Liquid Chromatography–Tandem Mass Spectrometry for Total and Unbound Concentrations in Human Plasma
Background: Pharmacokinetic studies and therapeutic drug monitoring of antibiotics require a simple, rapid, and reliable analytical method for monitoring the concentrations in plasma, including unbound concentrations for highly protein-bound drugs. The aim of the current work was to develop and validate a liquid chromatography–tandem mass spectrometry method for the simultaneous determination of total and unbound concentrations of 3 widely used β-lactam antibiotics (cefalexin, cefazolin, and flucloxacillin) and the often coadministered drug probenecid in human plasma, suitable for pharmacokinetic studies and f...
Source: Therapeutic Drug Monitoring - November 16, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research