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Therapeutic Drug Monitoring

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https://www.readbyqxmd.com/read/28107255/high-methotrexate-triglutamate-level-is-an-independent-predictor-of-adverse-effects-in-asian-indian-rheumatoid-arthritis-patients-a-preliminary-study
#1
Amit Sandhu, Varun Dhir, Archana Bhatnagar, Veena Dhawan, Jasbinder Kaur, Ankita Sood, Shankar Naidu, Shabeer Ahmad, Neelam Varma, Aman Sharma, Shefali Sharma
BACKGROUND: It is unclear whether erythrocyte methotrexate polyglutamate levels (MTX-glun) are associated with response or adverse effects to methotrexate in rheumatoid arthritis. This preliminary study evaluated their utility in Asian-Indian patients over 24 weeks. METHODS: Rheumatoid arthritis patients were started on oral methotrexate at a dose of 15 mg per week, which was escalated to 25 mg by 12 weeks and continued till 24 weeks. Erythrocyte (RBC) MTX-glu1 to MTX-glu5 levels (nmol/L RBC) were determined at 4, 8, 16, and 24 weeks by using reverse-phase high-performance liquid chromatography...
January 19, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28045783/quantitative-method-for-simultaneous-analysis-of-acetaminophen-and-six-metabolites
#2
Laureen A Lammers, Roos Achterbergh, Marcel C M Pistorius, Johannes A Romijn, Ron A A Mathôt
BACKGROUND: Hepatotoxicity after ingestion of high-dose acetaminophen (N-acetyl-para-aminophenol, APAP) is caused by the metabolites of the drug. To gain more insight in factors influencing susceptibility to APAP hepatotoxicity, quantification of APAP and metabolites is important. A few methods have been developed to simultaneously quantify APAP and its most important metabolites. However, these methods require a comprehensive sample preparation and long run times. The aim of this study was to develop and validate a simplified, but sensitive, method for the simultaneous quantification of acetaminophen, the main metabolites acetaminophen-glucuronide and acetaminophen-sulfate, and four Cytochrome P450-mediated metabolites by using liquid chromatography with mass spectrometric detection (LC-MS/MS)...
December 30, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28045782/fast-and-adequate-liquid-chromatography-tandem-mass-spectrometric-determination-of-z-endoxifen-serum-levels-for-therapeutic-drug-monitoring
#3
S de Krou, H Rosing, B Nuijen, J H M Schellens, J H Beijnen
BACKGROUND: Z-endoxifen (further referred to as endoxifen, unless stated otherwise) is proposed as the most important metabolite of tamoxifen. Patients receiving adjuvant tamoxifen treatment with endoxifen levels below the threshold of 5.9 ng/mL may have an increased risk of breast cancer recurrence. Several factors, such as genetic polymorphisms, drug interactions, and (non-)adherence, lead to large inter-patient variability in endoxifen exposure, resulting in a substantial number of patients showing sub therapeutic levels...
December 30, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28045781/improved-open-well-stability-of-acmia-reagent-for-determining-blood-tacrolimus
#4
Yoshiharu Suzuki, Keisuke Kohno, Kosuke Doki, Nobuhiro Ohkohchi, Masato Homma
No abstract text is available yet for this article.
December 30, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28045862/comparing-azole-plasma-trough-levels-in-lung-transplant-recipients-percentage-of-therapeutic-levels-and-intra-patient-variability
#5
Daniela Stelzer, Alexandra Weber, Franziska Ihle, Sandhya Matthes, Felix Ceelen, Gregor Zimmermann, Nikolaus Kneidinger, Rene Schramm, Hauke Winter, Michael Zoller, Michael Vogeser, Juergen Behr, Claus Neurohr
BACKGROUND: This study compared therapeutic azole plasma trough levels (APL) of the azole antimycotics itraconazole (ITR), voriconazole (VOR), and posaconazole (POS) in lung transplant recipients and analyzed the influencing factors. In addition, intra-patient variability for each azole was determined. METHODS: From July 2012 to July 2015, 806 APL of ITR, VOR, POS liquid (POS-Liq), and POS tablets (POS-Tab) were measured in 173 patients of the Munich Lung Transplantation (LTx) Program...
December 29, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28045861/pharmacokinetics-and-pharmacogenetics-of-ssris-during-pregnancy-an-observational-study
#6
Laura Pogliani, Felicia Stefania Falvella, Dario Cattaneo, Paola Pileri, Anna Flora Moscatiello, Stefania Cheli, Sara Baldelli, Valentina Fabiano, Irene Cetin, Emilio Clementi, Gianvincenzo Zuccotti
BACKGROUND: An involvement of selective serotonin reuptake inhibitors (SSRIs) in increasing the risk of malformations, neonatal withdrawal syndrome, has been suggested recently. Here, we aimed to investigate the contribution of individual pharmacogenetics of SSRI on infants' outcome. We also estimated the umbilical/maternal plasma SSRI concentration ratio in the pregnant women still on SSRI therapy at the time of delivery. METHODS: Thirty-four pregnant women, referred to our hospital from January 2011 to July 2015, who were given SSRIs in the third trimester, and related children, were considered...
December 29, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28033162/an-ex-vivo-model-to-decipher-the-impact-of-extracorporeal-membrane-oxygenation-on-beta-lactam-degradation-kinetics
#7
Cyril Leven, Pierre Fillâtre, Antoine Petitcollin, Marie-Clémence Verdier, Jérôme Laurent, Nicolas Nesseler, Yoann Launey, Pierre Tattevin, Eric Bellissant, Erwan Flécher, Florian Lemaitre
BACKGROUND: As a consequence of drug sequestration, increase in volume of distribution or alteration of elimination, extracorporeal membrane oxygenation (ECMO) might lead to inadequate plasma concentrations of vital drugs. The aim of this experimental study was to develop an ex vivo model to better characterize the impact of ECMO procedure on beta-lactam antibiotics pharmacokinetics. METHODS: Plasma concentrations of cefotaxime, ceftazidime, cefepime, piperacillin, oxacillin, amoxicillin, and ceftriaxone were measured in an ex vivo ECMO circuit primed with whole human blood and compared to controls stored in glass tubes and polyvinyl chloride (PVC) tubing...
December 23, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28030535/development-of-a-limited-sampling-strategy-for-the-estimation-of-exposure-to-high-dose-etoposide-after-intravenous-infusion-in-pediatric-patients
#8
Dorota Danielak, Joanna Sobiak, Jacek Wachowiak, Franciszek Główka, Maria Chrzanowska
BACKGROUND: Etoposide (VP-16), a podophylotoxin derivative, is used in conditioning regimens prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with acute lymphoblastic leukemia (ALL). The aim of this study was to develop a limited sampling strategy (LSS) suitable for the prediction of exposure to VP-16 defined as area-under-time-concentration curve (AUC). METHODS: The study included 28 pediatric patients with ALL, who were administered a 4h infusion of 60 mg/kg VP-16...
December 20, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27941536/lc-ms-ms-analysis-of-erythrocyte-thiopurine-nucleotides-and-their-association-with-genetic-variants-in-patients-with-neuromyelitis-optica-spectrum-disorders-taking-azathioprine
#9
Shenghui Mei, Xindi Li, Xiaoqing Gong, Xingang Li, Li Yang, Heng Zhou, Yonghong Liu, Anna Zhou, Leting Zhu, Xinghu Zhang, Zhigang Zhao
BACKGROUND: Azathioprine (AZA) is a first-line drug in treating neuromyelitis optica spectrum disorders (NMOSD). To exhibit its bioactivity, AZA needs to be converted to thiopurine nucleotides (TPNs) including 6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-MMPNs) that are affected by genetic polymorphisms. This study aims to develop an LC-MS/MS method for the analysis of erythrocyte concentrations of TPNs and to evaluate their associations with variants of various genes (MTHFR, TPMT, HLA, SLC29A1, SLC28A2, SLC28A3, ABCB1 and ABCC4) in patients with NMOSD...
November 29, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27941535/estimation-of-mycophenolic-acid-area-under-the-curve-with-limited-sampling-strategy-in-chinese-renal-transplant-recipients-receiving-enteric-coated-mycophenolate-sodium
#10
Yichen Jia, Bo Peng, Long Li, Jina Wang, Xuanchuan Wang, Guisheng Qi, Ruiming Rong, Liming Wang, Jianxin Qiu, Ming Xu, Tongyu Zhu
BACKGROUND: The enteric-coated mycophenolate sodium (EC-MPS), whose active constituent is mycophenolic acid (MPA), has been widely clinically used for organ transplant recipients. However, its absorption is delayed due to its special designed dosage form, which results in difficulty to monitor the exposure of the MPA in patients receiving the EC-MPS. This study was aimed at developing a relatively practical and precise model with limited sampling strategy (LSS) to estimate the 12-hour area under the concentration-time curve (AUC0-12 h) of MPA for Chinese renal transplant recipients receiving EC-MPS...
November 29, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27898598/pharmacokinetics-of-mycophenolic-acid-and-dose-optimization-in-children-after-intestinal-transplantation
#11
Caroline Barau, Antonio Mellos, Stéphanie Chhun, Florence Lacaille, Valérie Furlan
BACKGROUND: Mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (MPS) are now commonly used in pediatric intestinal transplantation (Tx), but to date, no clear recommendations regarding the dosing regimen have been made in this population. The aim of this study was to determine the MMF/MPS dosage required to achieve an area under the plasma concentration-time curve from 0 to 12 hours (AUC0-12) for mycophenolic acid (MPA) greater than 30 mg.h/L in children after intestinal transplantation...
November 28, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27861314/effect-of-the-direct-oral-anticoagulants-rivaroxaban-and-apixaban-on-the-disposition-of-calcineurin-inhibitors-in-transplant-recipients
#12
Thomas Vanhove, Isabel Spriet, Pieter Annaert, Johan Maertens, Johan Van Cleemput, Robin Vos, Dirk Kuypers
BACKGROUND: Calcineurin inhibitors (CNIs) and direct oral anticoagulants (DOACs) share certain metabolic pathways, but whether DOACs influence CNI exposure has not been assessed. METHODS: A single-center retrospective analysis was performed including 39 organ recipients treated with the combination of a CNI and rivaroxaban (n = 29) or apixaban (n = 10). Dose-corrected CNI trough concentrations (C0/D) during 200 days before and after DOAC initiation were recorded (n = 261), together with covariates known to influence CNI disposition such as steroid dose and hematocrit...
November 17, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27861318/prediction-of-an-optimal-dose-of-aripiprazole-in-the-treatment-of-schizophrenia-from-plasma-concentrations-of-aripiprazole-plus-its-active-metabolite-dehydroaripiprazole-at-week-1
#13
Goyo Nagai, Kazuo Mihara, Akifumi Nakamura, Kenji Nemoto, Shoko Kagawa, Takeshi Suzuki, Tsuyoshi Kondo
BACKGROUND: It has been suggested that a plasma trough concentration of aripiprazole plus its active metabolite, dehydroaripiprazole of 225 ng/mL is a threshold for a good therapeutic response in the treatment of acutely exacerbated patients with schizophrenia. The present study investigated whether or not an optimal dose of aripiprazole could be predicted from these concentrations at week 1. METHODS: The subjects were 26 inpatients with schizophrenia, who received aripiprazole once a day for three weeks...
November 16, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27861317/development-and-validation-of-a-simultaneous-quantification-method-of-fourteen-tyrosine-kinase-inhibitors-in-human-plasma-using-lc-ms-ms
#14
Huu-Hien Huynh, Claire Pressiat, Hélène Sauvageon, Isabelle Madelaine, Patricia Maslanka, Céleste Lebbé, Catherine Thieblemont, Lauriane Goldwirt, Samia Mourah
BACKGROUND: A sensitive LC-MS/MS method for the analysis in a small volume of plasma of 14 tyrosine kinase inhibitors (TKIs) currently used (imatinib, dasatinib, ibrutinib, ponatinib, trametinib, sunitinib, cobimetinib, dabrafenib, erlotinib, lapatinib, nilotinib, bosutinib, sorafenib, and vemurafenib) has been developed and validated. This multi-analyte LC-MS/MS assay is of interest for anticancer drug combination therapy. METHODS: After a simple protein precipitation of plasma samples, the chromatographic separation was performed using a UPLC system coupled with MS/MS in a positive ionization mode...
November 16, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27861316/development-of-an-uhplc-uv-method-for-quantification-of-direct-oral-anticoagulants-apixaban-rivaroxaban-dabigatran-and-its-prodrug-dabigatran-etexilate-in-human-serum
#15
Sebastian Boehr, Ekkehard Haen
BACKGROUND: Direct oral anticoagulants (DOACs) currently have no indication for monitoring even though there are data that imply that individual dosing can improve and add safety to the therapy. METHODS: An ultra-high performance liquid chromatography (UHPLC) method with ultra violet (UV) detection has been developed and validated for apixaban, dabigatran, dabigatran etexilate, and rivaroxaban. Protein precipitation with methanol (1:3 vol/vol) was used as sample preparation...
November 16, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27861315/brincidofovir-is-not-a-substrate-for-the-human-organic-anion-transporter-1-oat1-a-mechanistic-explanation-for-the-lack-of-nephrotoxicity-observed-in-clinical-studies
#16
Timothy K Tippin, Marion E Morrison, Thomas M Brundage, Hervé Momméja-Marin
BACKGROUND: Brincidofovir (BCV) is an orally bioavailable lipid conjugate of cidofovir with increased in vitro potency relative to cidofovir against all five families of double-stranded DNA viruses that cause human disease. Following intravenous (IV) administration of cidofovir, the organic anion transporter 1 (OAT1) transports cidofovir from the blood into the renal proximal tubule epithelial cells with resulting dose-limiting nephrotoxicity. OBJECTIVE: To study whether OAT1 transports BCV and to evaluate the pharmacokinetic and renal safety profile of oral BCV compared with IV cidofovir...
November 16, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28081042/detection-of-hydrocodone-and-morphine-as-metabolites-in-oral-fluid-by-lc-ms-ms-in-patients-prescribed-codeine
#17
Robert E West, Maria G Guevara, Charles Mikel, Ruben Gamez
A retrospective analysis of oral fluid drug testing results using LC-MS/MS was performed to determine the prevalence rates in oral fluid for codeine (COD) and 3 COD metabolites-morphine (MOR), norhydrocodone (NHC), and hydrocodone (HCOD). Oral fluid samples were collected using Quantisal oral fluid collection device (Immunalysis Inc.) and submitted to Millennium Health, LLC for the routine drug analysis by LC-MS/MS. Consistent with previously published literature, COD was the primary analyte detected in oral fluid after the use of COD...
February 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28081041/a-systematic-literature-review-approach-to-estimate-the-therapeutic-index-of-selected-immunosuppressant-drugs-after-renal-transplantation
#18
Jessica E Ericson, Kanecia O Zimmerman, Daniel Gonzalez, Chiara Melloni, Jeffrey T Guptill, Kevin D Hill, Huali Wu, Michael Cohen-Wolkowiez
BACKGROUND: Drugs that exhibit close margins between therapeutic and toxic blood concentrations are considered to have a narrow therapeutic index (NTI). The Food and Drug Administration has proposed that NTI drugs should have more stringent bioequivalence standards for approval of generic formulations. However, many immunosuppressant drugs do not have a well-defined therapeutic index (TI). METHODS: We sought to determine whether safety, efficacy, and pharmacokinetic data obtained from the medical literature through a comprehensive literature search could be used to estimate the TI of cyclosporine, tacrolimus, and sirolimus...
February 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28081040/azathioprine-therapy-in-a-pediatric-tpmt-deficient-patient-still-an-option
#19
S A W van Moorsel, N Bevers, M Meurs, L K van Rossum, P M Hooymans, D R Wong
We describe the case of a pediatric patient on azathioprine therapy with previously undiagnosed homozygote thiopurine S-methyltransferase (TPMT) deficiency, resulting in myelotoxic thiopurine metabolite levels. The patient was successfully treated with a very low azathioprine dose of 50 mg once a week (4% of standard dose), guided by frequent thiopurine metabolite measurement and a close clinical surveillance. We demonstrate that azathioprine therapy still might be an effective and safe therapeutic option in pediatric thiopurine S-methyltransferase-deficient IBD patients...
February 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28030534/single-nucleotide-polymorphism-of-cyp3a5-impacts-the-exposure-to-tacrolimus-in-pediatric-renal-transplant-recipients-a-pharmacogenetic-substudy-of-the-twist-trial
#20
Heiko Billing, Britta Höcker, Alexander Fichtner, Rita van Damme-Lombaerts, Styrbjorn Friman, Jenö Jaray, Karel Vondrak, Eniko Sarvary, Luca Dello Strologo, Michael Oellerich, Nicolas von Ahsen, Burkhard Tönshoff
BACKGROUND: The pharmacokinetics of tacrolimus (TAC) and mycophenolic acid (MPA) are highly variable. An impact of single-nucleotide polymorphisms (SNPs) of the genes coding for enzymes and transporters involved in the pharmacokinetics of TAC and/or MPA is intuitively conceivable. Accordingly, we sought to analyze the influence of different SNPs on TAC and MPA exposure in pediatric renal transplant recipients. METHODS: A subpopulation of 37 patients (median age: 12...
November 24, 2016: Therapeutic Drug Monitoring
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