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Proficiency Testing for Meropenem and Piperacillin Therapeutic Drug Monitoring: Preliminary Results From the Belgian Society on Infectiology and Clinical Microbiology Pharmacokinetic–Pharmacodynamic Working Group
No abstract available (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Letter to the Editor Source Type: research

Comparison of Antifactor Xa and Activated Partial Thromboplastin Time Monitoring for Heparin Dosing in Vascular Surgery Patients: A Single-Center Retrospective Study
Conclusions: The use of anti-Xa levels for heparin titration showed higher rates of major bleeding complications in vascular surgery patients compared with aPTT monitoring, but no significant difference was identified in this study. Vascular surgery patients with relatively high aPTT to anti-Xa values may have an increased risk of bleeding complications when heparin is titrated based on anti-Xa levels. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Clozapine and Norclozapine Concentrations in Paired Human Plasma and Serum Samples
Conclusions: Despite the finding that clozapine and norclozapine were significantly higher in plasma than in serum when obtained from blood collected into Vacuette serum separator collection tubes, this difference is insignificant in the clinical interpretation of clozapine and norclozapine TDM results. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Influence of Renal Function on Pharmacokinetics of Antiepileptic Drugs Metabolized by CYP3A4 in a Patient With Renal Impairment
Background: Several studies have demonstrated that renal impairment not only decreases renal clearance but also hepatic clearance of medications that are CYP3A4 substrates. We evaluated the influence of renal function on the pharmacokinetics of antiepileptic drugs metabolized by CYP3A4. Methods: We retrospectively calculated the concentration/dose ratio (CD ratio) for topiramate and clobazam in an epilepsy patient with renal impairment. In addition, we determined the CD ratio of perampanel in 17 patients with normal renal function and compared it with that in the patient with renal impairment. Results: A patient wi...
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Comparison of the ARK Immunoassay With High-Performance Liquid Chromatography With Ultraviolet Detection for Therapeutic Drug Monitoring of Linezolid
Conclusions: Acceptable analytical performance of the ARK LZD immunoassay has been demonstrated both with spiked QC and patients' samples, making it a viable alternative to HPLC for the therapeutic drug monitoring of LZD in clinical practice in laboratory hospitals that do not have HPLC equipment. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Lack of Detection of New Amphetamine-Like Drugs Using Conventional Urinary Immunoassays
Conclusions: The available immunoassays lack sensitivity to detect 4-FA and PMMA in lower urine concentrations. Awareness of the fact that novel DOA may lead to false-negative urinary drug tests is of great importance. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Influence of Comedication on Levetiracetam Pharmacokinetics
Conclusions: Comedication with EIAEDs increased LEV CL/F by more than 40%, whereas carbamazepine had the greatest inducing potency with LEV CL/F being 81% higher than that of the monotherapy group. These data suggest that monitoring LEV serum concentration during polytherapy with EIAEDs is indicated. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

External Evaluation of Population Pharmacokinetic Models of Infliximab in Patients With Inflammatory Bowel Disease
Conclusions: While simulation-based diagnostics provided unsatisfactory results, the prediction-based diagnostics demonstrate that the population pharmacokinetic model developed by Fasanmade et al for CD can be used to predict and design individualized IFX dose regimens that meet the individual needs of patients with CD and ulcerative colitis. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Early Therapeutic Drug Monitoring of Posaconazole Oral Suspension in Patients With Hematologic Malignancies
Background: Therapeutic drug monitoring (TDM) of posaconazole is usually performed 1 week after starting the drug because of its long half-life. However, previous studies showed that measuring the posaconazole plasma concentration (PPC) on day 3 is effective for predicting steady-state levels. The purpose of this study was to evaluate the relevance of early TDM (day 3) of posaconazole for achieving an optimal PPC. Methods: This prospective study was conducted from September 2014 to August 2016. A total of 148 patients with acute myeloid leukemia or myelodysplastic syndromes received a 200 mg posaconazole oral suspensi...
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Relationship Between Initial Vancomycin Trough Levels and Early-Onset Vancomycin-Associated Nephrotoxicity in Critically Ill Patients
We examined the relationship between initial VCM trough levels and early-onset VCM-associated nephrotoxicity. Methods: We performed a retrospective study of patients who had therapeutic drug monitoring of VCM with initial trough levels within 4 days after the beginning of VCM administration. We excluded patients who received renal replacement therapy from 2 days before to 7 days after the beginning of VCM administration, were younger than 18 years, or had renal dysfunction before the beginning of VCM administration. Early-onset VCM-associated nephrotoxicity was defined as an increase in serum creatinine level of ≥0.5...
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Comparative Analysis of Ampicillin Plasma and Dried Blood Spot Pharmacokinetics in Neonates
Background: Dried blood spot (DBS) is a practical sampling strategy for pharmacokinetic studies in neonates. The utility of DBS to determine the population pharmacokinetics (pop-PK) of ampicillin, as well as accuracy versus plasma samples, was evaluated. Methods: An open-label, multicenter, opportunistic, prospective study was conducted in neonates. Ampicillin concentrations from plasma and DBS (CONCPlasma and CONCDBS) were measured by liquid chromatographic tandem mass spectrometry and analyzed using pop-PK and statistical (including transformation) approaches. Results: A total of 29 paired plasma and DBS samples ...
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Therapeutic Drug Monitoring of Asparaginase Activity—Method Comparison of MAAT and AHA Test Used in the International AIEOP-BFM ALL 2009 Trial
Conclusions: Comparison of the MAAT and AHA test for PEG-ASE activity confirmed a mean difference of 23% between MAAT and AHA test for PEG-ASE activities between 30 and 600 U/L. The discrepancy increased in samples with>600 U/L PEG-ASE activity, which will be especially relevant when evaluating high PEG-ASE activities in relation to toxicity, efficacy, and population pharmacokinetics. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Therapeutic Drug Monitoring of Busulfan for the Management of Pediatric Patients: Cross-Validation of Methods and Long-Term Performance
Conclusions: We conclude that TDM is an effective method of achieving targeted Bu levels in children. QC programs are crucial to monitoring and maintaining the quality of an analytical method. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Plasma 7-Hydroxymethotrexate Levels Versus Methotrexate to Predict Delayed Elimination in Children Receiving High-Dose Methotrexate
Background: The aim of this study was to investigate the correlation between 7-hydroxymethotrexate (7-OHMTX) and creatinine and to evaluate the predictive value of 7-OHMTX levels on delayed elimination at 24 and 48 hours. In addition, differences in methotrexate (MTX), 7-OHMTX levels, and MTX metabolism using the ratio MTX/7-OHMTX were determined according to age. Methods: The authors included a total of 106 cycles, corresponding to 33 patients (mean age: 9.8 years, range: 2–18 years) suffering from acute lymphoblastic leukemia, non-Hodgkin lymphoma and osteosarcoma and receiving high-dose MTX (HD-MTX). Plasma M...
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Ultra–High Performance Liquid Chromatography Tandem Mass Spectrometry for Cyclosporine Analysis in Human Whole Blood and Comparison With an Antibody-Conjugated Magnetic Immunoassay
Conclusions: A rapid, simple, accurate, and reliable UHPLC-MS/MS method for CsA analysis in human whole blood was developed, validated, and applied in 85 samples. On average, 21.1% overestimation was observed in ACMIA compared with that in the UHPLC-MS/MS. Further and larger studies are required to identify whether this degree of variance could be accepted by clinicians. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Multicenter Evaluation of a New Electrochemiluminescence Immunoassay for Everolimus Concentrations in Whole Blood
Conclusions: Based on these results, the Roche Elecsys everolimus ECLIA can be considered suitable for routine therapeutic drug monitoring. A positive bias was observed with respect to LC-MS/MS methods, suggesting that it may be necessary to rebaseline individual patients when switching from LC-MS/MS to the ECLIA; however, this must also be considered for any change of method for everolimus measurement. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Adequacy of Initial Everolimus Dose, With and Without Calcineurin Inhibitors, in Kidney Transplant Recipients
This study investigates the adequacy of initial everolimus (EVR) dose, with and without calcineurin inhibitors (CNI), in kidney transplant recipients. Methods: This retrospective cohort analysis involved data from 305 kidney transplant recipients participating in 3 randomized trials receiving reduced dose cyclosporin A (CsA) combined with EVR 0.75 mg BID (CSA/EVR0.75, N = 32) or 1.5 mg BID (CSA/EVR1.5, N = 31), reduced dose tacrolimus (TAC) combined with EVR 1.5 mg BID (TAC0.05/EVR1.5, N = 83), standard dose TAC combined with EVR 1.5 mg BID (TAC0.1/EVR1.5, N = 93), and EVR 1.5 mg BID (EVR1.5, N = 66) with TAC introducti...
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Acute Intoxications and Fatalities From Illicit Fentanyl and Analogues: An Update
Abstract: Illicit fentanyl and its analogues are very dangerous synthetic opioids, with high abuse potential and severe adverse effects including coma and death. They are used as adulterants in street heroin, cocaine, and methamphetamine, or as heroin substitutes sold to unaware users with a high risk of overdoses. Fentanyl and its analogues have also been identified in counterfeit medicinal products, such as oxycodone, hydrocodone, and alprazolam tablets, or as components of speedball mixtures together with cocaine or other stimulants. In recent years, a number of epidemics involving acute intoxications and deaths relat...
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Review Article Source Type: research

Systematic Review of Salivary Versus Blood Concentrations of Antituberculosis Drugs and Their Potential for Salivary Therapeutic Drug Monitoring
Conclusions: For gatifloxacin and linezolid, salivary therapeutic drug monitoring is likely possible due to a narrow range of saliva–plasma and saliva–serum ratios. For isoniazid, rifampicin, moxifloxacin, ofloxacin, and clarithromycin, salivary therapeutic drug monitoring might be possible; however, a large variability in saliva–plasma and saliva–serum ratios was observed. Unfortunately, salivary therapeutic drug monitoring is probably not possible for doripenem and amoxicillin/clavulanate, as a result of very low salivary drug concentrations. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Review Article Source Type: research

Companion and Complementary Diagnostics–Focus on PD-L1 Expression Assays for PD-1/PD-L1 Checkpoint Inhibitors in Non–Small Cell Lung Cancer
Abstract: Over the last couple of decades, molecular diagnostics have played an increasing role in drug development. Especially within oncology, more and more drugs are being developed together with a predictive biomarker assay using the drug-diagnostic codevelopment model. Not only do these assays support the development process but also the use of the drugs after regulatory approval as an important treatment decision tool. When these predictive biomarker assays are linked to a specific drug, they are called companion diagnostics. Furthermore, these assays are also considered an important element in the realization of p...
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Review Article Source Type: research

Enhancement and Suppression of Ionization in Drug Analysis Using HPLC-MS/MS in Support of Therapeutic Drug Monitoring: A Review of Current Knowledge of Its Minimization and Assessment
Abstract: High-performance liquid chromatography coupled with tandem mass spectrometry is commonly used for quantitation of analytes in biological matrices, because of the selectivity, sensitivity, and high throughput offered by this technique. However, the presence of both suppression and enhancement of ionization (SEI) by matrix components is an increasingly recognized impediment to accurate results. The existence of SEI indicates that ionization efficiency is a result of the chemical environment seen by both the analyte and internal standard during ion formation. SEI is influenced by the type and the make of ion sourc...
Source: Therapeutic Drug Monitoring - January 17, 2018 Category: Drugs & Pharmacology Tags: Review Article Source Type: research

Proficiency Testing for Meropenem and Piperacillin Therapeutic Drug Monitoring: Preliminary Results From the Belgian Society on Infectiology and Clinical Microbiology Pharmacokinetic–Pharmacodynamic Working Group
No abstract available (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Letter to the Editor Source Type: research

Comparison of Antifactor Xa and Activated Partial Thromboplastin Time Monitoring for Heparin Dosing in Vascular Surgery Patients: A Single-Center Retrospective Study
Conclusions: The use of anti-Xa levels for heparin titration showed higher rates of major bleeding complications in vascular surgery patients compared with aPTT monitoring, but no significant difference was identified in this study. Vascular surgery patients with relatively high aPTT to anti-Xa values may have an increased risk of bleeding complications when heparin is titrated based on anti-Xa levels. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Clozapine and Norclozapine Concentrations in Paired Human Plasma and Serum Samples
Conclusions: Despite the finding that clozapine and norclozapine were significantly higher in plasma than in serum when obtained from blood collected into Vacuette serum separator collection tubes, this difference is insignificant in the clinical interpretation of clozapine and norclozapine TDM results. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Influence of Renal Function on Pharmacokinetics of Antiepileptic Drugs Metabolized by CYP3A4 in a Patient With Renal Impairment
Background: Several studies have demonstrated that renal impairment not only decreases renal clearance but also hepatic clearance of medications that are CYP3A4 substrates. We evaluated the influence of renal function on the pharmacokinetics of antiepileptic drugs metabolized by CYP3A4. Methods: We retrospectively calculated the concentration/dose ratio (CD ratio) for topiramate and clobazam in an epilepsy patient with renal impairment. In addition, we determined the CD ratio of perampanel in 17 patients with normal renal function and compared it with that in the patient with renal impairment. Results: A patient wi...
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Comparison of the ARK Immunoassay With High-Performance Liquid Chromatography With Ultraviolet Detection for Therapeutic Drug Monitoring of Linezolid
Conclusions: Acceptable analytical performance of the ARK LZD immunoassay has been demonstrated both with spiked QC and patients' samples, making it a viable alternative to HPLC for the therapeutic drug monitoring of LZD in clinical practice in laboratory hospitals that do not have HPLC equipment. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Lack of Detection of New Amphetamine-Like Drugs Using Conventional Urinary Immunoassays
Conclusions: The available immunoassays lack sensitivity to detect 4-FA and PMMA in lower urine concentrations. Awareness of the fact that novel DOA may lead to false-negative urinary drug tests is of great importance. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Influence of Comedication on Levetiracetam Pharmacokinetics
Conclusions: Comedication with EIAEDs increased LEV CL/F by more than 40%, whereas carbamazepine had the greatest inducing potency with LEV CL/F being 81% higher than that of the monotherapy group. These data suggest that monitoring LEV serum concentration during polytherapy with EIAEDs is indicated. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

External Evaluation of Population Pharmacokinetic Models of Infliximab in Patients With Inflammatory Bowel Disease
Conclusions: While simulation-based diagnostics provided unsatisfactory results, the prediction-based diagnostics demonstrate that the population pharmacokinetic model developed by Fasanmade et al for CD can be used to predict and design individualized IFX dose regimens that meet the individual needs of patients with CD and ulcerative colitis. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Early Therapeutic Drug Monitoring of Posaconazole Oral Suspension in Patients With Hematologic Malignancies
Background: Therapeutic drug monitoring (TDM) of posaconazole is usually performed 1 week after starting the drug because of its long half-life. However, previous studies showed that measuring the posaconazole plasma concentration (PPC) on day 3 is effective for predicting steady-state levels. The purpose of this study was to evaluate the relevance of early TDM (day 3) of posaconazole for achieving an optimal PPC. Methods: This prospective study was conducted from September 2014 to August 2016. A total of 148 patients with acute myeloid leukemia or myelodysplastic syndromes received a 200 mg posaconazole oral suspensi...
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Relationship Between Initial Vancomycin Trough Levels and Early-Onset Vancomycin-Associated Nephrotoxicity in Critically Ill Patients
We examined the relationship between initial VCM trough levels and early-onset VCM-associated nephrotoxicity. Methods: We performed a retrospective study of patients who had therapeutic drug monitoring of VCM with initial trough levels within 4 days after the beginning of VCM administration. We excluded patients who received renal replacement therapy from 2 days before to 7 days after the beginning of VCM administration, were younger than 18 years, or had renal dysfunction before the beginning of VCM administration. Early-onset VCM-associated nephrotoxicity was defined as an increase in serum creatinine level of ≥0.5...
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Comparative Analysis of Ampicillin Plasma and Dried Blood Spot Pharmacokinetics in Neonates
Background: Dried blood spot (DBS) is a practical sampling strategy for pharmacokinetic studies in neonates. The utility of DBS to determine the population pharmacokinetics (pop-PK) of ampicillin, as well as accuracy versus plasma samples, was evaluated. Methods: An open-label, multicenter, opportunistic, prospective study was conducted in neonates. Ampicillin concentrations from plasma and DBS (CONCPlasma and CONCDBS) were measured by liquid chromatographic tandem mass spectrometry and analyzed using pop-PK and statistical (including transformation) approaches. Results: A total of 29 paired plasma and DBS samples ...
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Therapeutic Drug Monitoring of Asparaginase Activity—Method Comparison of MAAT and AHA Test Used in the International AIEOP-BFM ALL 2009 Trial
Conclusions: Comparison of the MAAT and AHA test for PEG-ASE activity confirmed a mean difference of 23% between MAAT and AHA test for PEG-ASE activities between 30 and 600 U/L. The discrepancy increased in samples with>600 U/L PEG-ASE activity, which will be especially relevant when evaluating high PEG-ASE activities in relation to toxicity, efficacy, and population pharmacokinetics. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Therapeutic Drug Monitoring of Busulfan for the Management of Pediatric Patients: Cross-Validation of Methods and Long-Term Performance
Conclusions: We conclude that TDM is an effective method of achieving targeted Bu levels in children. QC programs are crucial to monitoring and maintaining the quality of an analytical method. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Plasma 7-Hydroxymethotrexate Levels Versus Methotrexate to Predict Delayed Elimination in Children Receiving High-Dose Methotrexate
Background: The aim of this study was to investigate the correlation between 7-hydroxymethotrexate (7-OHMTX) and creatinine and to evaluate the predictive value of 7-OHMTX levels on delayed elimination at 24 and 48 hours. In addition, differences in methotrexate (MTX), 7-OHMTX levels, and MTX metabolism using the ratio MTX/7-OHMTX were determined according to age. Methods: The authors included a total of 106 cycles, corresponding to 33 patients (mean age: 9.8 years, range: 2–18 years) suffering from acute lymphoblastic leukemia, non-Hodgkin lymphoma and osteosarcoma and receiving high-dose MTX (HD-MTX). Plasma M...
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Ultra–High Performance Liquid Chromatography Tandem Mass Spectrometry for Cyclosporine Analysis in Human Whole Blood and Comparison With an Antibody-Conjugated Magnetic Immunoassay
Conclusions: A rapid, simple, accurate, and reliable UHPLC-MS/MS method for CsA analysis in human whole blood was developed, validated, and applied in 85 samples. On average, 21.1% overestimation was observed in ACMIA compared with that in the UHPLC-MS/MS. Further and larger studies are required to identify whether this degree of variance could be accepted by clinicians. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Multicenter Evaluation of a New Electrochemiluminescence Immunoassay for Everolimus Concentrations in Whole Blood
Conclusions: Based on these results, the Roche Elecsys everolimus ECLIA can be considered suitable for routine therapeutic drug monitoring. A positive bias was observed with respect to LC-MS/MS methods, suggesting that it may be necessary to rebaseline individual patients when switching from LC-MS/MS to the ECLIA; however, this must also be considered for any change of method for everolimus measurement. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Adequacy of Initial Everolimus Dose, With and Without Calcineurin Inhibitors, in Kidney Transplant Recipients
This study investigates the adequacy of initial everolimus (EVR) dose, with and without calcineurin inhibitors (CNI), in kidney transplant recipients. Methods: This retrospective cohort analysis involved data from 305 kidney transplant recipients participating in 3 randomized trials receiving reduced dose cyclosporin A (CsA) combined with EVR 0.75 mg BID (CSA/EVR0.75, N = 32) or 1.5 mg BID (CSA/EVR1.5, N = 31), reduced dose tacrolimus (TAC) combined with EVR 1.5 mg BID (TAC0.05/EVR1.5, N = 83), standard dose TAC combined with EVR 1.5 mg BID (TAC0.1/EVR1.5, N = 93), and EVR 1.5 mg BID (EVR1.5, N = 66) with TAC introducti...
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Acute Intoxications and Fatalities From Illicit Fentanyl and Analogues: An Update
Abstract: Illicit fentanyl and its analogues are very dangerous synthetic opioids, with high abuse potential and severe adverse effects including coma and death. They are used as adulterants in street heroin, cocaine, and methamphetamine, or as heroin substitutes sold to unaware users with a high risk of overdoses. Fentanyl and its analogues have also been identified in counterfeit medicinal products, such as oxycodone, hydrocodone, and alprazolam tablets, or as components of speedball mixtures together with cocaine or other stimulants. In recent years, a number of epidemics involving acute intoxications and deaths relat...
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Review Article Source Type: research

Systematic Review of Salivary Versus Blood Concentrations of Antituberculosis Drugs and Their Potential for Salivary Therapeutic Drug Monitoring
Conclusions: For gatifloxacin and linezolid, salivary therapeutic drug monitoring is likely possible due to a narrow range of saliva–plasma and saliva–serum ratios. For isoniazid, rifampicin, moxifloxacin, ofloxacin, and clarithromycin, salivary therapeutic drug monitoring might be possible; however, a large variability in saliva–plasma and saliva–serum ratios was observed. Unfortunately, salivary therapeutic drug monitoring is probably not possible for doripenem and amoxicillin/clavulanate, as a result of very low salivary drug concentrations. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Review Article Source Type: research

Companion and Complementary Diagnostics–Focus on PD-L1 Expression Assays for PD-1/PD-L1 Checkpoint Inhibitors in Non–Small Cell Lung Cancer
Abstract: Over the last couple of decades, molecular diagnostics have played an increasing role in drug development. Especially within oncology, more and more drugs are being developed together with a predictive biomarker assay using the drug-diagnostic codevelopment model. Not only do these assays support the development process but also the use of the drugs after regulatory approval as an important treatment decision tool. When these predictive biomarker assays are linked to a specific drug, they are called companion diagnostics. Furthermore, these assays are also considered an important element in the realization of p...
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Review Article Source Type: research

Enhancement and Suppression of Ionization in Drug Analysis Using HPLC-MS/MS in Support of Therapeutic Drug Monitoring: A Review of Current Knowledge of Its Minimization and Assessment
Abstract: High-performance liquid chromatography coupled with tandem mass spectrometry is commonly used for quantitation of analytes in biological matrices, because of the selectivity, sensitivity, and high throughput offered by this technique. However, the presence of both suppression and enhancement of ionization (SEI) by matrix components is an increasingly recognized impediment to accurate results. The existence of SEI indicates that ionization efficiency is a result of the chemical environment seen by both the analyte and internal standard during ion formation. SEI is influenced by the type and the make of ion sourc...
Source: Therapeutic Drug Monitoring - January 12, 2018 Category: Drugs & Pharmacology Tags: Review Article Source Type: research

Effect of N-Desalkylquetiapine/Quetiapine Plasma Level Ratio on Anxiety and Depression in Bipolar Disoder: A Prospective Observational Study: Erratum
No abstract available (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - November 13, 2017 Category: Drugs & Pharmacology Tags: Erratum Source Type: research

Evaluation of a Novel Immunoassay for Lacosamide Therapeutic Drug Monitoring: Comparison With a Liquid Chromatography-Mass Spectrometry Assay
Conclusions: The performance of the new ARK method on the Architect system is acceptable and may be used routinely to measure serum lacosamide concentration in the clinic although the nature of the bias has to be carefully addressed. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - November 13, 2017 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Serum Concentrations of Paliperidone After Administration of the Long-Acting Injectable Formulation
Conclusions: The data show a 4-fold interindividual difference in dose-adjusted serum concentrations within the 10–90 percentile range and illustrate the significant effects of age and p-glycoprotein induction on the pharmacokinetics of paliperidone. The study also indicates that at least in some patients, it might take longer time than anticipated to reach steady state. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - November 13, 2017 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Comparison of Dried Blood Spots Versus Conventional Plasma Collection for the Characterization of Efavirenz Pharmacokinetics in a Large-Scale Global Clinical Trial—The ENCORE1 Study
Background: The aim of this study was to determine the utility of dried blood spots (DBS) compared with conventional plasma collection methods for characterization of efavirenz pharmacokinetics, in the setting of a large-scale, global clinical trial (ENCORE1). Methods: Six hundred thirty patients were recruited from 38 sites and had single matched whole blood DBS and plasma samples (mid-dose interval) taken at weeks 4 and 12 of treatment. In addition, a subgroup of patients underwent intensive DBS and plasma sampling (0–24 hours) to provide full-profile data for pharmacokinetic parameters. Efavirenz concentrations w...
Source: Therapeutic Drug Monitoring - November 13, 2017 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Development of a Liquid Chromatography–Tandem Mass Spectrometric Method for Quantification of Mycophenolic Acid and Its Glucuronides in Dried Blood Spot Samples
Conclusions: We developed and validated a liquid chromatography/electrospray ionization–tandem mass spectrometry method for analysis of MPA in DBS samples. The method is useful for monitoring the MPA blood level. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - November 13, 2017 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Comparison of Biological Screening and Diagnostic Indicators to Detect In Utero Opiate and Cocaine Exposure Among Mother–Infant Dyads
Conclusions: Alternative indicators collected at delivery were ineffective at identifying in utero substance exposure, especially neonatal-exposed ICD-9-CM codes. Low sensitivity scores indicate that many exposed neonates could be misdiagnosed or left untreated. Accurate antenatal exposure identification at delivery is an important form of tertiary assessment that warrants the development of improved screening methodology and standardization of hospital biological drug testing. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - November 13, 2017 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Enoxaparin Population Pharmacokinetics in the First Year of Life
Conclusions: Dosing of enoxaparin in infants younger than 1 year should incorporate PMA. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - November 13, 2017 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Validated LC-MS/MS Method for the Simultaneous Determination of Amlodipine and Its Major Metabolites in Human Plasma of Hypertensive Patients
Conclusions: The present method with acceptable analytical performance can be helpful for monitoring the plasma concentration of AML, including the determination of its metabolites in patients with hypertension. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - November 13, 2017 Category: Drugs & Pharmacology Tags: Original Article Source Type: research