Temporal Stability Evaluation of Drugs in Plasma on Primary Sampling Tube
No abstract available (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Letters to the Editor Source Type: research

Distribution of Genetic Polymorphisms of Genes Implicated in Thiopurine Drugs Metabolism
Abstract: Thiopurine-S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) are crucial enzymes involved in the metabolism of thiopurine drugs. Significant interethnic variation in the expression of TPMT and ITPA is caused by single nucleotide polymorphisms of genes encoding these proteins. The aim of this study was to describe the distribution of TPMT and ITPA polymorphisms in healthy Tunisian subjects and to establish the metabolizer status of thiopurine drugs in this population. A total of 309 healthy Tunisian subjects were recruited among blood donors of Fattouma Bourguiba Hospital of Monastir. A ...
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Pharmacokinetic Comparison of Two Mycophenolate Mofetil Formulations in Kidney Transplant Recipients
Conclusions: PK parameters of the 2 MPA drugs were comparable in early renal transplant patients in this study. The 2 formulations were well tolerated in Chinese kidney transplant patients. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Evaluation of an Ion Trap Toxtyper Liquid Chromatography With An Ion Trap Mass Spectrometric Instrument (Toxtyper) for Drug of Abuse Screening in Oral Fluid
Background: Oral fluid (OF) is increasingly used as an alternative sample matrix in drug of abuse screening. Screening is commonly performed by immunoassays and results confirmed using laborious gas chromatography–mass spectrometry (GC-MS)–based methods. Therefore, an easy to operate ion trap mass spectrometric (IT-MS) commercial screening method (Toxtyper; Bruker Daltronik, Bremen, Germany) combined with a laboratory-developed sample preparation procedure has been evaluated for their application to OF. Methods: OF samples were subjected to protein precipitation followed by HybridSPE-Phospholipid extractio...
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Age- and Bodyweight-dependent Allometric Exponent Model for Scaling Clearance and Maintenance Dose of Theophylline From Neonates to Adults
The objective of this study is to develop and evaluate single-exponent, bodyweight-dependent allometric exponent (BDE), age-dependent exponent (ADE), and segmented regression models for predicting clearance and maintenance dose of theophylline. Methods: The BDE model was described by the following equation: JOURNAL/thdm/04.02/00007691-201810000-00014/math_14MM1/v/2018-09-13T063150Z/r/image-tiff , where L × BW−M defines the BDE for clearance. The coefficient and the exponents L and M were estimated. The ADE model consisted of several empirical exponents based on age and ranged from 0.75 (children>5 year...
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Influence of Sex, Age, and Weight on Levetiracetam Pharmacokinetics
Background: Levetiracetam (LEV) is a second-generation antiepileptic drug extensively used in therapeutics. The aim of this study was to evaluate the influence that sex, age, and weight exert on LEV pharmacokinetics in clinical practice. Methods: We conducted a 6-year retrospective observational study. Patients were classified in subgroups according to sex, weight (normal range, overweight, and obese), and age (young adult: 16–30 years old, middle-aged adult: 31–50 years old, advanced adult: 51–64 years old, and elderly adult: ≥65 years old). We compared LEV apparent oral clearance (LEV CL/F) betw...
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Influence of Dose and Antiepileptic Comedication on Lacosamide Serum Concentrations in Patients With Epilepsy of Different Ages
Conclusions: In accordance with previous therapeutic drug monitoring studies, our results confirmed that enzyme inducers reduce the LCM trough serum concentrations by 30%–40%. In children, the effects of comedication are more pronounced but should be confirmed by further studies. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

An Improved LC-ESI-MS/MS Method to Quantify Pregabalin in Human Plasma and Dry Plasma Spot for Therapeutic Monitoring and Pharmacokinetic Applications
Conclusions: Proposed method involves simple and rapid steps of sample processing that do not require a precolumn or postcolumn derivatization procedure. The method is suitable for routine pharmacokinetic analysis and therapeutic monitoring of PGB. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

A Common mdr1 Gene Polymorphism is Associated With Changes in Linezolid Clearance
Conclusions: The obtained results suggest the possible influence of ABCB1 in linezolid pharmacokinetics, bringing new interest for pharmacogenetic analyses in antimicrobial chemotherapy. These analyses could be incorporated in therapeutic protocols for precision medicine, including a combined use of genetic evaluation (for starting dose) and follow-up therapeutic drug monitoring. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Development of an Enzyme-Linked Immune Sorbent Assay to Measure Nivolumab and Pembrolizumab Serum Concentrations
Conclusions: The in-house–developed ELISA provides the opportunity to measure both nivolumab and pembrolizumab serum concentrations. This may help identify possible ER relationships in treated cancer patients and may potentially lead to dose adjustments in the future. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Simple LC-MS/MS Methods Using Core–Shell Octadecylsilyl Microparticulate for the Quantitation of Total and Free Daptomycin in Human Plasma
Conclusions: The present simple method with an acceptable analytical performance can be helpful for monitoring the pharmacokinetics of daptomycin in infected patients observed in clinical settings. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Population Pharmacokinetic Analysis of Gentamicin in Pediatric Extracorporeal Membrane Oxygenation
Conclusions: Fat-free mass should be used to dose gentamicin in pediatric ECMO patients. Serum creatinine is a marker of gentamicin clearance and should be used to adjust gentamicin dosing in pediatric ECMO patients. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Pharmacokinetics Evaluation of Mycophenolic Acid and Its Glucuronide Metabolite in Chinese Renal Transplant Recipients Receiving Enteric-Coated Mycophenolate Sodium and Tacrolimus
Conclusions: The pharmacokinetic profile of total and free MPA and its main metabolite MPAG was examined in Chinese adult renal transplant patients receiving EC-MPS. The use of LSS to estimate individual free and total MPA exposure could be useful in optimizing patient care. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Clinically Relevant Effect of UGT1A4*3 on Lamotrigine Serum Concentration Is Restricted to Postmenopausal Women—A Study Matching Therapeutic Drug Monitoring and Genotype Data From 534 Patients
Background: Previous studies have reported inconsistent findings regarding the impact of the UGT1A4*3 variant allele on lamotrigine (LTG) exposure. As no studies have controlled for nongenetic factors, the aim of this study was to compare serum concentrations of LTG in carriers versus noncarriers of UGT1A4*3 adjusting for differences in age, sex, and valproic acid (VPA) comedication. Methods: Matched data on serum concentration of LTG and UGT1A4 genotype patients with known information about VPA comedication were included retrospectively from a therapeutic drug monitoring service. Linear mixed-model analysis was used ...
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Longitudinal Study of Tacrolimus in Lymphocytes During the First Year After Kidney Transplantation
Introduction: Tacrolimus (TAC) is an immunosuppressive drug used after organ transplantation. Dosing is adjusted using whole blood (WB-TAC) measurements. Patients within the therapeutic WB-TAC window still experience rejections and adverse effects. Alternative monitoring methods are therefore warranted. The authors developed a method for measuring TAC in peripheral blood mononuclear cell (PBMC) isolates (PBMC-TAC) and performed a pharmacokinetic study in a cohort of kidney transplant patients during the first year after transplantation. Methods: PBMCs were isolated from whole blood by gradient centrifugation. After me...
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Impact of POR and CYP3A5 Polymorphisms on Trough Concentration to Dose Ratio of Tacrolimus in the Early Post-operative Period Following Kidney Transplantation
The objective of this study was to explore the interaction between POR*28 and CYP3A5*3 polymorphisms and their main effects on tacrolimus trough concentration to dose ratios on day 7 after kidney transplantation. Methods: Two hundred sixteen adult kidney transplant recipients participated in this retrospective study. All participants received a twice daily tacrolimus regimen. Blood samples and data were collected on day 7 after transplantation. A 2-way analysis of covariance was performed. Tested covariates were age, hemoglobin, serum albumin, and prednisolone dose. Results: A 2 × 2 analysis of covariance revea...
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Therapeutic Drug Monitoring of Antiepileptic Drugs in Epilepsy: A 2018 Update
Conclusions: TDM provides a pragmatic approach to epilepsy care, in that bespoke dose adjustments are undertaken based on drug concentrations so as to optimize clinical outcome. For the older first-generation AEDs (carbamazepine, ethosuximide, phenobarbital, phenytoin, primidone, and valproic acid), much data have accumulated in this regard. However, this is occurring increasingly for the new AEDs (brivaracetam, eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, piracetam, pregabalin, rufinamide, stiripentol, sulthiame, tiagabine, topiramate, vigabatrin, and...
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Review Article Source Type: research

Liquid Biopsies to Monitor Solid Organ Transplant Function: A Review of New Biomarkers
Abstract: Despite modern immunosuppressive therapy, allograft rejection remains a major cause of solid organ transplant dysfunction. For clinical care, organ transplant function is routinely monitored by measuring biomarkers that, depending on the organ transplanted, include serum creatinine, N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP), and aspartate aminotransferase. All can be measured easily in clinical chemistry laboratories. The main problem with these biomarkers is that they have a low sensitivity for the detection of allograft damage and are nonspecific for the detection of allograft rejection....
Source: Therapeutic Drug Monitoring - September 14, 2018 Category: Drugs & Pharmacology Tags: Review Article Source Type: research

Development and Validation of a Chromatographic Ultraviolet Method for the Quantification of Isavuconazole in Human Plasma Samples
No abstract available (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Letters to the Editor Source Type: research

Time-Dependent Decline in Serum Phenytoin Concentration With Heightened Convulsive Seizure Risk by Prolonged Administration of Fosphenytoin in Japanese: A Retrospective Study
Conclusions: Prolonged use of fosphenytoin, for such patients as those with autoimmune-mediated encephalopathy accompanied with reflux disease and/or ileus, time dependently decreased the serum concentration of phenytoin and increased the risk of convulsion. Therefore, the maintenance dose should be increased to maintain the therapeutic serum concentration. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Validation of an Isavuconazole High-Performance Liquid Chromatography Assay in Plasma for Routine Therapeutic Drug Monitoring Applications
Background: Isavuconazole is a triazole antifungal agent for treatment of invasive aspergillosis and mucormycosis. At present, it is unclear whether a therapeutic drug monitoring (TDM) of isavuconazole would be necessary. The aim of the investigation was to validate a high-performance liquid chromatography (HPLC) assay for routine applications. Methods: An HPLC assay for routine determination of isavuconazole in plasma has been adapted and validated. The assay used the reagents and HPLC column provided by the ChromSystems HPLC Kit for TDM of itraconazole, posaconazole, and voriconazole. Isocratic flow rate was set at ...
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Preliminary Evidence for Enhanced Thymine Absorption: A Putative New Phenotype Associated With Fluoropyrimidine Toxicity in Cancer Patients
Conclusions: This small cohort provided evidence for a hypothesis that fluorouracil toxicity cases may include a previously undescribed pyrimidine absorption variant, “enhanced thymine absorption,” and elevated THY/DHT ratios in urine may predict fluorouracil toxicity. A prospective study is currently being conducted. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Methadone Maintenance Treatment: A 15-year Retrospective Study in Split-Dalmatia County, Croatia
Conclusions: The results of this study show the favorable epidemiological trend because of the decreasing number of new opiate patients in treatment. The retention of opiate patients in substitution therapy indicates the effectiveness of methadone maintenance programs. Our research did not determine any influence of methadone substitution therapy on an increasing risk of specific (overdose) mortality. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

A Liquid Chromatography-Mass Spectrometry Assay for Determination of Perampanel and Concomitant Antiepileptic Drugs in the Plasma of Patients With Epilepsy Compared With a Fluorescent HPLC Assay
Conclusions: The assay allows for highly sensitive and selective quantification of perampanel and concomitant AEDs in patient plasma samples and can be easily implemented in clinical settings. Our findings are in agreement with previously published data in patients comedicated with enzyme inducer AEDs, but seem to indicate a possible interaction in patients treated with the enzyme inhibitor drug valproic acid. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Development and Validation of an Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry Method for the Concurrent Measurement of Gabapentin, Lamotrigine, Levetiracetam, Monohydroxy Derivative of Oxcarbazepine, and Zonisamide Concentrations in Serum in a Clinical Setting
This study presents the development and validation of a clinical ultra-performance liquid chromatography–MS/MS method for the concurrent measurement of gabapentin, lamotrigine, levetiracetam, monohydroxy derivative of oxcarbazepine, and zonisamide in human serum. Methods: To determine the optimal assay analyte range, one year of AED therapeutic drug monitoring results (n = 1825) were evaluated. Simple protein precipitation with acetonitrile containing isotopically labeled internal standards was used. Reverse-phase ultra-performance liquid chromatography chromatographic separation was used, having a total run time ...
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Comparison of CYP3A4-Inducing Capacity of Enzyme-Inducing Antiepileptic Drugs Using 4β-Hydroxycholesterol as Biomarker
Background: Enzyme-inducing antiepileptic drugs (EIAEDs) are among the clinically most important inducers of cytochrome P450 (CYP) 3A4, but there is limited evidence regarding the comparative potency of each EIAED in raising CYP3A4 activity. The aim of this study was to estimate CYP3A4-inductive potency of EIAEDs by comparing CYP3A4 activity in patients treated with carbamazepine, phenobarbital, or phenytoin. Methods: Residual serum samples from patients treated with EIAEDs or levetiracetam were collected from a therapeutic drug monitoring service for analysis of 4β-hydroxycholesterol (4βOHC), which is an in...
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Impact of Drug Interactions on Clobazam and N-Desmethylclobazam Concentrations in Pediatric Patients With Epilepsy
This study characterizes the impact of CYP3A4 and CYP2C19 drug interactions on CLB and NCLB serum concentrations (Cp) and concentration/dose (Cp/D) ratios in pediatric patients with epilepsy. Methods: This was a retrospective chart review including patients older than 1 month, who received CLB between April 2012 and March 2017. Extracted data included patient demographics, CLB daily dose, CLB and NCLB Cp, calculated CLB and NCLB Cp/Cp and Cp/D ratios, and all concomitant drugs. Results: The study included 995 CLB concentration sets from 302 patients (median age 7.6 years and range 0.2–40.1 years). Pharmacokinet...
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Effect of Valproate and Antidepressant Drugs on Clozapine Metabolism in Patients With Psychotic Mood Disorders
Background: The aim of the present study was to appraise retrospectively the influence of valproate (VPA) and antidepressants (ADs) on the steady-state plasma concentrations of clozapine (CLZ), the prototype of various second-generation antipsychotics, norclozapine (NCLZ, its main metabolite), and their ratio (NCLZ:CLZ). Methods: Sixty-seven psychotic patients with a prevalent diagnosis of bipolar disorder were studied. We then analyzed data altogether and subdivided them into 4 groups, according to pharmacological treatments: #1 CLZ (n = 21), #2 CLZ plus ADs (n = 13), #3 CLZ plus VPA (n = 16), and #4 CLZ plus ADs plu...
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Interindividual and Intraindividual Variation of Methylphenidate Concentrations in Serum and Saliva of Patients With Attention-Deficit/Hyperactivity Disorder
Background: Therapeutic drug monitoring is becoming increasingly important in psychiatric therapy, especially in children. However, for several reasons, it cannot yet be implemented as a daily routine in clinical or outpatient settings. To evaluate new, noninvasive procedures, blood and saliva (oral fluid) samples were collected from patients with attention-deficit/hyperactivity disorder (ADHD) who were also being administered methylphenidate (MPH). The study's main purposes were to correlate MPH concentrations in serum and saliva between subjects and to analyze intraindividual variation of serum concentration. Methods:...
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Pharmacokinetics of Doripenem in Healthy Koreans and Monte Carlo Simulations to Explore Optimal Dosage Regimens in Patients With Normal and Enhanced Renal Function
Conclusions: These results suggest that dosage adjustment such as increasing the dose or lengthening the infusion time should be considered in patients with normal or enhanced renal function. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Simultaneous Quantification of Adalimumab and Infliximab in Human Plasma by Liquid Chromatography–Tandem Mass Spectrometry
Conclusions: This LC-MS/MS method can be used for the quantification of ADA and IFX in a single analytical run and for the optimization of LC-MS/MS resource use in clinical pharmacology laboratories. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Development of an Abbreviated Mycophenolic Acid Area Under the Time–Concentration Curve for Renal Transplant Patients Under Enteric-Coated Mycophenolate Sodium: A Comparison With Critical Analysis of Available Equations
Conclusions: This analysis offers blood-sampling alternatives for MPA monitoring depending on the precision needed. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Survival Time to Biopsy-Proven Acute Rejection and Tacrolimus Adverse Drug Reactions in Pediatric Liver Transplantation
This study aimed to identify peritransplant predictors of AR and factors related to the risk of ADR to tacrolimus in a large Latin American cohort of pediatric liver transplant patients. Methods: We performed a retrospective cohort study in a pediatric liver transplant population (n = 72). Peritransplant variables were collected retrospectively including demographic, clinical, laboratory parameters, genomic (CYP3A5 donor and recipients polymorphism), and tacrolimus trough concentrations (C0) over a 2-year follow-up period. Variability in tacrolimus C0 was calculated using percent coefficient of variation and tortuosity....
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Large-Scale Variability of Inpatient Tacrolimus Therapeutic Drug Monitoring at an Academic Transplant Center: A Retrospective Study
Conclusions: Based on this large single-center study, the authors concluded that the inpatient TDM process is prone to timing errors, thus is financially wasteful, and at its worst harmful to patients due to clinical decisions being made on the basis of unreliable data. Further work is needed on systems solutions to better align the laboratory study collection and drug administration processes. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Mass Spectrometry for Research and Application in Therapeutic Drug Monitoring or Clinical and Forensic Toxicology
This article reviews current applications of various hyphenated low- and high-resolution mass spectrometry techniques in the field of therapeutic drug monitoring and clinical/forensic toxicology in both research and practice. They cover gas chromatography, liquid chromatography, matrix-assisted laser desorption ionization, or paper spray ionization coupled to quadrupole, ion trap, time-of-flight, or Orbitrap mass analyzers. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Review Article Source Type: research

Eltrombopag-Induced Acute Liver Failure in a Pediatric Patient: A Pharmacokinetic and Pharmacogenetic Analysis
We presented the case study of a 3-year-old girl with chronic ITP. She arrived in the pediatric intensive care unit with acute liver failure due to eltrombopag toxicity despite taking the standard drug dosage. A very high eltrombopag plasma concentration, indicating drug toxicity, was found through TDM. The patient also carried the allelic variations that are involved in drug metabolism [CYP2C8 and UDP glucuronosyltransferase (UGT) 1A1 (UGT1A1)] and drug cellular transportation [ABCG2 (ATP-binding cassette G2)]. This observation highlights the importance of using TDM and pharmacogenetic approaches to manage patients' unusu...
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Grand Rounds Source Type: research

Therapeutic Drug Monitoring of Methotrexate in Plasma Using Ultra High-Performance Liquid Chromatography–Electrospray Ionization–Tandem Mass Spectrometry: Necessary After Administration of Glucarpidase in Methotrexate Intoxications
We present 2 children treated with HD-MTX and afterward treated with glucarpidase at different time-points after their HD-MTX infusions. After the administration of glucarpidase, a nontoxic metabolite of MTX cross-reacts with MTX in the standard immunoassay (Abbott Diagnostics, Hoofddorp, the Netherlands) resulting in an artificially elevated MTX level. An artificially elevated MTX level results in unnecessarily long folinic acid administration, which decreases the effectivity of MTX. This grand round highlights the importance of measuring plasma MTX levels after the administration of glucarpidase with an ultra high-perfor...
Source: Therapeutic Drug Monitoring - July 11, 2018 Category: Drugs & Pharmacology Tags: Grand Rounds Source Type: research

The relation between dosage, serum concentrations, and clinical outcome in children and adolescents treated with sertraline: a naturalistic study Erratum
No abstract available (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 11, 2018 Category: Drugs & Pharmacology Tags: Erratum Source Type: research

Cocaine Detection in Maternal and Neonatal Hair: Implications to Fetal Toxicology Expression of Concern
No abstract available (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 11, 2018 Category: Drugs & Pharmacology Tags: Erratum Source Type: research

Vancomycin Area Under the Curve Simplified
Conclusions: Troughs of 15–20 mg/L are rarely needed for organisms with an MIC of 1 mg/L or less. AUC24:MIC goals of greater than 400 can best be achieved with higher doses in mg/kg while targeting lower troughs. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 11, 2018 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Quantification of Apixaban, Dabigatran, Edoxaban, and Rivaroxaban in Human Serum by UHPLC-MS/MS—Method Development, Validation, and Application
Conclusions: The developed method fulfilled the set validation criteria, and its suitability was demonstrated in a routine setting. The instability of edoxaban may complicate the transport of routine samples to the laboratory. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Warfarin Dosing According to the Genotype-guided Algorithm is Most Beneficial in Patients With Atrial Fibrillation: A Randomized Parallel Group Trial
Conclusions: CYP2C9 and VKORC1 genotype-guided dosing of warfarin may be beneficial in patients diagnosed with AF. There is no evidence for such conclusion in patients with DVT and PE. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Effects of Cytochrome P450 (CYP) 2C19 Genotypes on Steady-State Plasma Concentrations of Escitalopram and its Desmethyl Metabolite in Japanese Patients With Depression
Conclusions: These findings suggest that the CYP2C19 variants are associated with steady-state plasma concentrations of escitalopram to some extent but are not associated with desmethylescitalopram. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Serum and Saliva Concentrations of Venlafaxine, O-Desmethylvenlafaxine, Quetiapine, and Citalopram in Psychiatric Patients
Background: Therapeutic drug monitoring has become increasingly important in psychiatric therapy. However, it is not yet implemented as a daily routine in clinical settings. To evaluate new, noninvasive procedures, we compared blood and saliva venlafaxine, quetiapine, and citalopram concentrations in samples collected from psychiatric patients. Methods: We collected blood and saliva samples from 75 psychiatric patients (39 venlafaxine, 19 quetiapine, and 17 citalopram). Saliva sampling was achieved by the use of cotton pads. Venlafaxine (and its metabolite O-desmethylvenlafaxine) and quetiapine were analyzed by LC-MS/...
Source: Therapeutic Drug Monitoring - May 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Dried Blood Spot Analysis for Therapeutic Drug Monitoring of Antipsychotics: Drawbacks of Its Clinical Application
Conclusions: The DBS method to quantify risperidone, aripiprazole, pipamperone, and their major metabolites did not meet the acceptance criteria in the Bland–Altman analyses. Therefore, this DBS method was not clinically valid. This study shows the importance of a clinical validation study with use of Bland–Altman plots before clinical implementation. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Development and Validation of a Simultaneous Quantification Method of Ruxolitinib, Vismodegib, Olaparib, and Pazopanib in Human Plasma Using Liquid Chromatography Coupled With Tandem Mass Spectrometry
Conclusions: Using liquid chromatography coupled with tandem mass spectrometry, we have developed and validated a simple and rapid assay for the simultaneous quantification of olaparib, vismodegib, pazopanib, and ruxolitinib in human plasma. This method is now part of our therapeutic drug monitoring service provision and is currently used clinically to manage patients prescribed these drugs. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Measurement of Teicoplanin Concentration With Liquid Chromatography-Tandem Mass Spectrometry Method Demonstrates the Usefulness of Therapeutic Drug Monitoring in Hematologic Patient Populations
Conclusions: Based on these results, the present UHPLC-MS/MS method can be considered suitable for routine TDM of teicoplanin. Also, based on the insufficient trough teicoplanin concentrations achieved with standard dose regimen, and the higher trough teicoplanin concentrations achieved with TDM-guided individualized dose regimen, this study highlights the importance of TDM of teicoplanin, especially in high-risk patient groups. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

The “Ideal” Body Weight for Pediatric Gentamicin Dosing in the Era of Obesity: A Population Pharmacokinetic Analysis
Conclusions: FFM should be used to adjust ABW for empirically dosing gentamicin in pediatric patients aged 2–18 years. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Exploring the Use of C-Reactive Protein to Estimate the Pharmacodynamics of Vancomycin
Background: C-reactive protein (CRP) pharmacodynamic (PD) models have the potential to provide adjunctive methods for predicting the individual exposure response to antimicrobial therapy. We investigated CRP PD linked to a vancomycin pharmacokinetic (PK) model using routinely collected data from noncritical care adults in secondary care. Methods: Patients receiving intermittent intravenous vancomycin therapy in secondary care were identified. A 2-compartment vancomycin PK model was linked to a previously described PD model describing CRP response. PK and PD parameters were estimated using a Non-Parametric Adaptive Gri...
Source: Therapeutic Drug Monitoring - May 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Effect of Extracorporeal Membrane Oxygenation on the New Vancomycin Dosing Regimen in Critically Ill Patients Receiving Continuous Venovenous Hemofiltration
Conclusions: All patients receiving CVVH achieved the target Ctrough with this new dosing regimen, but those with concurrent ECMO did not. Ctrough must be more closely monitored in patients using ECMO simultaneously. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 11, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research