Development of an Enzyme-Linked Immune Sorbent Assay to Measure Nivolumab and Pembrolizumab Serum Concentrations.

Abstract:

BACKGROUND:Treatment with monoclonal antibodies (mAbs) against programmed cell death protein 1 receptor is subject to high variation in treatment outcome among cancer patients. For these agents, no exposure-response (ER) relationships have been investigated in routine health care settings. However, ER relationships have been identified for several other mAbs used in oncology. Methods to conveniently measure serum concentrations of anti-programmed cell death protein 1 mAbs in routine health care may clarify possible ER relationships. Therefore, the authors aimed to develop an enzyme-linked immune sorbent assay (ELISA) for the measurement of both nivolumab and pembrolizumab serum concentrations of treated cancer patients. METHODS:Optimal capture antigen and detection antibody concentrations were selected based on titrations. Nivolumab calibration standards ranging from 0.2 to 300 ng/mL were tested in duplicate. Accuracy was assessed in 2 recovery experiments. Intra- and interassay variations were assessed on 3 different days by 2 independent technicians. The developed ELISA was also set up for pembrolizumab calibration curves. Cross-reactivity of nivolumab measurements with ipilimumab was assessed. Of one nivolumab treated patient, serum concentrations in follow up samples were measured and presented. RESULTS:Nivolumab calibration standards of 0.20-25 ng/mL were used. Nivolumab trough concentrations after 1 cycle in 8 patients ranged from 17.3 to 31.1 mcg/mL. The range of accuracy was 84%-105%, whereas intra- and interassay variations showed a coefficient of variation of 5.5% and 10.1%, respectively. No cross-reactivity with ipilimumab was detected. Pembrolizumab trough concentrations (n = 8) ranged from 9.1 to 19.7 mcg/mL after 1 infusion. 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.

journal_name

Ther Drug Monit

authors

Basak EA,Wijkhuijs AJM,Mathijssen RHJ,Koolen SLW,Schreurs MWJ

doi

10.1097/FTD.0000000000000534

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

596-601

issue

5

eissn

0163-4356

issn

1536-3694

journal_volume

40

pub_type

杂志文章
  • Safe management of tacrolimus together with posaconazole in lung transplant patients with cystic fibrosis.

    abstract::Oral posaconazole (PSZ), an azole antifungal drug, was recently introduced for the treatment of invasive fungal infections. The prescription of PSZ together with the immunosuppressant tacrolimus (TRL) was evaluated in 14 lung transplant patients with cystic fibrosis. PSZ inhibited CYP3A4 TRL metabolism, resulting in a...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/FTD.0b013e31819de6fd

    authors: Berge M,Chevalier P,Benammar M,Guillemain R,Amrein C,Lefeuvre S,Boussaud V,Billaud EM

    更新日期:2009-06-01 00:00:00

  • Therapeutic drug monitoring of theophylline in frail elderly patients: oral compared with nasogastric tube administration.

    abstract:SUMMARY:Treating debilitated elderly patients through nasogastric tube (NGT) can change the pharmacokinetic characteristics of drugs, mainly those that are slow released (SR). The purpose of this study was to compare pharmacokinetic parameters between patients who receive SR theophylline orally and those who receive it...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/00007691-200210000-00003

    authors: Berkovitch M,Dafni O,Leiboviz A,Mayan H,Habut B,Segal R

    更新日期:2002-10-01 00:00:00

  • Mycophenolic acid plasma concentrations: influence of comedication.

    abstract::Mycophenolate mofetil (MMF) in combination with cyclosporine (CsA) or Tacrolimus (TAC) has been show to be a potent immunosuppressive agent. The authors assessed the mycophenolic acid (MPA) plasma levels achieved in clinical practice and evaluated the effect of concomitant administration of CsA and TAC . One hundred f...

    journal_title:Therapeutic drug monitoring

    pub_type: 临床试验,杂志文章

    doi:10.1097/00007691-200102000-00007

    authors: Pou L,Brunet M,Cantarell C,Vidal E,Oppenheimer F,Monforte V,Vilardell J,Roman A,Martorell J,Capdevila L

    更新日期:2001-02-01 00:00:00

  • Analysis of isepamicin in human plasma by radioimmunoassay, microbiologic assay, and high-performance liquid chromatography.

    abstract::Plasma concentrations of isepamicin, a new aminoglycoside antibiotic, were determined by radioimmunoassay (RIA), microbiological assay (MA), and high-performance liquid chromatography (HPLC) in healthy volunteers after administration of 7.5 mg/kg intramuscular dosages once daily for 10 days. Plasma samples were collec...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/00007691-199712000-00012

    authors: Lin CC,Veals J,Korduba C,Hilbert MJ,Nomeir A

    更新日期:1997-12-01 00:00:00

  • Determination of pentamidine in whole blood, plasma, and urine by high-performance liquid chromatography.

    abstract::The analysis of pentamidine in whole blood, plasma, and urine by liquid chromatography is described. Extraction was made with a mixture of acetonitrile and chloroform followed by back-extraction into phosphate buffer. A reversed-phase chromatographic system with fluorescence detection was used. The precision of the me...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/00007691-199007000-00011

    authors: Ericsson O,Rais M

    更新日期:1990-07-01 00:00:00

  • Dosage adjustment of high-dose methotrexate using Bayesian estimation: a comparative study of two different concentrations at the end of 8-h infusions.

    abstract::Bayesian estimation (BE) of pharmacokinetic parameters enables the clinician to adjust the dosage of high-dose methotrexate (HDMTX) to correct the inter- and intraindividual variation of concentrations that are responsible for severe toxicity. In this study of 672 HDMTX infusions, we validated an approach that consist...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/00007691-199510000-00007

    authors: Pignon T,Lacarelle B,Duffaud F,Guillet P,Catalin J,Durand A,Favre R

    更新日期:1995-10-01 00:00:00

  • Reliable and Easy-To-Use Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Analysis of Fluconazole, Isavuconazole, Itraconazole, Hydroxy-Itraconazole, Posaconazole, and Voriconazole in Human Plasma and Serum.

    abstract:BACKGROUND:A fast and easy-to-use liquid chromatography-tandem mass spectrometry method for the determination and quantification of 6 triazoles [fluconazole (FLZ), isavuconazole (ISZ), itraconazole (ITZ), hydroxy-itraconazole (OH-ITZ), posaconazole (PSZ), and voriconazole (VRZ)] in human plasma and serum was developed ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/FTD.0000000000000438

    authors: Müller C,Gehlen D,Blaich C,Prozeller D,Liss B,Streichert T,Wiesen MHJ

    更新日期:2017-10-01 00:00:00

  • Can saliva replace plasma for the monitoring of methadone?

    abstract::The aims of this study were to determine the relationship between saliva and plasma methadone concentrations and the influence of variability in saliva pH. Saliva and plasma samples were taken before the daily dose of methadone in 60 patients undergoing methadone maintenance treatment (MMT). Saliva pH was measured imm...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/01.ftd.0000164392.01779.db

    authors: Shiran MR,Hassanzadeh-Khayyat M,Iqbal MZ,Lagundoye O,Seivewright N,Lennard MS,Tucker GT,Rostami-Hodjegan A

    更新日期:2005-10-01 00:00:00

  • Light-induced racemization: artifacts in the analysis of the diastereoisomeric pairs of thioridazine 5-sulfoxide in the plasma and urine of patients treated with thioridazine.

    abstract::The ring sulfoxidation of thioridazine (THD), a widely used neuroleptic agent, yields two diastereoisomeric pairs, fast- and slow-eluting (FE and SE) thioridazine 5-sulfoxide (THD 5-SO). Until now, studies in which concentrations of these metabolites were measured in THD-treated patients have revealed no significant d...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:

    authors: Eap CB,Souche A,Koeb L,Baumann P

    更新日期:1991-07-01 00:00:00

  • Doping-control analysis of the 5alpha-reductase inhibitor finasteride: determination of its influence on urinary steroid profiles and detection of its major urinary metabolite.

    abstract::5alpha-Reductase inhibitors such as finasteride are prohibited in sports according to the World Anti-Doping Agency. This class of drugs is used therapeutically to treat benign prostatic hyperplasia, as well as male baldness, by decreasing 5alpha-reductase activity. Accordingly, metabolic pathways of endogenous as well...

    journal_title:Therapeutic drug monitoring

    pub_type: 临床试验,杂志文章

    doi:10.1097/FTD.0b013e31803bb85d

    authors: Thevis M,Geyer H,Mareck U,Flenker U,Schänzer W

    更新日期:2007-04-01 00:00:00

  • Serum levels of olanzapine and its N-desmethyl and 2-hydroxymethyl metabolites in child and adolescent psychiatric disorders: effects of dose, diagnosis, age, sex, smoking, and comedication.

    abstract::The aim of this study was to assess dose-related steady-state serum concentrations of olanzapine (OLZ) and its metabolites N-desmethyl OLZ (DMO) and 2-hydroxymethyl OLZ (2-OH-OLZ) (assessed by high-performance liquid chromatography) in 122 child and adolescent psychiatric patients (age 16.9 +/- 2.2, range, 10-21 years...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/01.ftd.0000249950.75462.7f

    authors: Theisen FM,Haberhausen M,Schulz E,Fleischhaker C,Clement HW,Heinzel-Gutenbrunner M,Remschmidt H

    更新日期:2006-12-01 00:00:00

  • Pharmacokinetic studies of rifampicin in the elderly.

    abstract::The pharmacokinetics of rifampicin (RMP) and its principal active metabolite desacetylrifampicin (DA-RMP) were studied in six subjects, ranging in age from 78 to 95 years, after single oral doses of 10 mg/kg RMP. The maximal plasma concentrations (Cmax) and the elimination half-lives (t 1/2 beta) of RMP are 8.83 +/- 1...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/00007691-198303000-00004

    authors: Advenier C,Gobert C,Houin G,Bidet D,Richelet S,Tillement JP

    更新日期:1983-01-01 00:00:00

  • Interference of oleandrin and oleandrigenin in digitoxin immunoassays: minimal cross reactivity with a new monoclonal chemiluminescent assay and high cross reactivity with the fluorescence polarization assay.

    abstract::Toxicity from ingestion of the oleander plant is common. Oleandrin, the oleander glycoside, has structural similarity to cardiac glycoside digoxin and is known to cross react with various digoxin immunoassays. The authors studied the cross reactivity of oleandrin and its deglycosylated congener oleandrigenin with a fl...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/00007691-199708000-00017

    authors: Datta P,Dasgupta A

    更新日期:1997-08-01 00:00:00

  • Nonparametric estimation of population characteristics of the kinetics of lithium from observational and experimental data: individualization of chronic dosing regimen using a new Bayesian approach.

    abstract::A population analysis of the kinetics of lithium was performed from experimental and observational data in 113 subjects in order to propose a new approach for lithium dosage individualization. The kinetics of lithium is described by a two-compartment model. Age, body weight, height, and serum creatinine are included a...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/00007691-199406000-00006

    authors: Taright N,Mentré F,Mallet A,Jouvent R

    更新日期:1994-06-01 00:00:00

  • Quantification of Delta9-tetrahydrocannabinol and its major metabolites in meconium by gas chromatographic-mass spectrometric assay: assay validation and preliminary results of the "meconium project".

    abstract::A rapid and simple procedure based on gas chromatography-mass spectrometry (GC-MS) is described for determination of Delta-tetrahydrocannabinol (THC), 11-hydroxy-Delta-tetrahydrocannabinol (THC-OH) and 11-nor-Delta-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in meconium using Delta-tetrahydrocannabinol (Delta-TH...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/01.ftd.0000245380.95186.13

    authors: Marchei E,Pellegrini M,Pacifici R,Palmi I,Lozano J,García-Algar O,Pichini S

    更新日期:2006-10-01 00:00:00

  • Lacosamide therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs.

    abstract:BACKGROUND:Lacosamide (LCM) is one of the newer antiepileptic drugs (AEDs) licensed as add-on treatment for partial epilepsy. Data on LCM pharmacokinetics and interactions are limited and partly contradictory. The purpose of this study was to assess the effect of concomitant AED therapy on steady state plasma concentra...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,随机对照试验

    doi:10.1097/FTD.0b013e318290eacc

    authors: Contin M,Albani F,Riva R,Candela C,Mohamed S,Baruzzi A

    更新日期:2013-12-01 00:00:00

  • A retrospective TDM database analysis of interpatient variability in the pharmacokinetics of lopinavir in HIV-infected adults.

    abstract::Lopinavir is one of the most-widely used protease inhibitors in the treatment of HIV-1 infected patients. Concentration-effect relationships have been described for both antiviral activity and toxicity. Less is known about patient characteristics that may determine interpatient variability in lopinavir plasma concentr...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/01.ftd.0000245681.12092.d6

    authors: van der Leur MR,Burger DM,la Porte CJ,Koopmans PP

    更新日期:2006-10-01 00:00:00

  • Development of a sensitive phospho-p70 S6 kinase ELISA to quantify mTOR proliferation signal inhibition.

    abstract:BACKGROUND:Drug blood levels can only serve as a surrogate because of the lack of information on the drug's direct pharmacological effects in the individual patient. Measurement of the mammalian target of rapamycin (mTOR) activity dependent on the phosphorylation status of p70 S6 kinase (p70 S6K) offers a practical way...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/FTD.0b013e3182804c9b

    authors: Hartmann B,He X,Keller F,Fischereder M,Guba M,Schmid H

    更新日期:2013-04-01 00:00:00

  • Thyroid medications during pregnancy.

    abstract::Euthyroid women experience dramatic changes in their thyroid physiology in order to accommodate the presence of placental and fetal tissues. These adaptations to the pregnant state make it crucial to develop reliable trimester-specific intervals for thyroid parameters. Use of non-pregnant reference intervals could lea...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,评审

    doi:10.1097/01.ftd.0000211834.41844.82

    authors: Bach-Huynh TG,Jonklaas J

    更新日期:2006-06-01 00:00:00

  • Population Pharmacokinetic Analysis of Meropenem in Critically Ill Patients With Acute Kidney Injury Treated With Continuous Hemodiafiltration.

    abstract:BACKGROUND:The aim of this study was to conduct a population pharmacokinetic (PK) analysis of meropenem and to explore the optimal dosing strategy for meropenem in critically ill patients with acute kidney injury receiving treatment with continuous hemodiafiltration (CHDF). METHODS:Blood samples were obtained on days ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/FTD.0000000000000741

    authors: Niibe Y,Suzuki T,Yamazaki S,Suzuki T,Takahashi N,Hattori N,Nakada TA,Oda S,Ishii I

    更新日期:2020-08-01 00:00:00

  • Possible interaction between cyclosporine and glibenclamide in posttransplant diabetic patients.

    abstract::The possible occurrence of a kinetic interaction between cyclosporine A and glibenclamide was assessed by reviewing data of six posttransplant diabetic patients who received the two drugs concurrently. Coadministration of the two drugs resulted in a 57% increase in the steady-state plasma cyclosporine levels despite n...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/00007691-199610000-00017

    authors: Islam SI,Masuda QN,Bolaji OO,Shaheen FM,Sheikh IA

    更新日期:1996-10-01 00:00:00

  • A sensitive gas chromatographic assay for amitriptyline and nortriptyline in plasma.

    abstract::A method for the quantitative determination of the tricyclic antidepressant drug amitriptyline (AT) and its active major metabolite, nortriptyline (NT), in plasma is described. The method involves a three-step extraction procedure, no derivatization, and a rapid run on a gas--liquid chromatograph equipped with a nitro...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/00007691-198212000-00006

    authors: Hals PA,Lundgren TI,Aarbakke J

    更新日期:1982-01-01 00:00:00

  • Theophylline clearance during and after mild upper respiratory infection.

    abstract::Theophylline clearance was estimated by a single-sample technique in 19 subjects with acute clinical respiratory infections. Mean (+/- SD) theophylline clearance during acute illness was 0.044 +/- 0.011 L X h-1 X kg-1 compared to 0.043 +/- 0.012 L X h-1 X kg-1 1 month later. In a subset of five subjects, single-sample...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/00007691-198709000-00005

    authors: Bachmann K,Schwartz J,Martin M,Jauregui L

    更新日期:1987-09-01 00:00:00

  • Routine methods in toxicology and therapeutic drug monitoring by high performance liquid chromatography. II. A rapid microscale method for determination of chloramphenicol in blood and cerebrospinal fluid.

    abstract::A highly sensitive, specific method for determining chloramphenicol levels in human blood plasma and cerebrospinal fluid is described. The method uses high performance liquid chromatography for the analysis, requires minimal quantities of patient specimen, and thus is suitable for use in newborn and pediatric patients...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/00007691-198709000-00016

    authors: Sood SP,Green VI,Bailey CL

    更新日期:1987-09-01 00:00:00

  • Metabolism and toxicologic analysis of tryptamine-derived drugs of abuse.

    abstract::5-Methoxy-N,N-dialkyltryptamines are tryptamine derivatives that possess strong hallucinogenic effects. Because of their escalating popularity and potent physiological effects, an increasing number of acute poisoning cases have been reported in various countries. For their metabolism in humans, only a few studies have...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/FTD.0b013e3181dcb40c

    authors: Katagi M,Kamata T,Zaitsu K,Shima N,Kamata H,Nakanishi K,Nishioka H,Miki A,Tsuchihashi H

    更新日期:2010-06-01 00:00:00

  • Dose adjustment strategy for oral microemulsion formulation of cyclosporine: population pharmacokinetics-based analysis in kidney transplant patients.

    abstract::The present study aims to determine the population pharmacokinetic parameters of cyclosporine (CsA) after multiple oral administration of the microemulsion formulation, Neoral, in kidney transplant patients and to propose a limited sampling strategy to predict AUC(0-4h) using them and the Bayesian method. The AUC(0-4h...

    journal_title:Therapeutic drug monitoring

    pub_type: 临床试验,杂志文章

    doi:10.1097/00007691-200406000-00012

    authors: Tokui K,Kimata T,Uchida K,Yuasa H,Hayashi Y,Itatsu T,Nabeshima T

    更新日期:2004-06-01 00:00:00

  • Multiple-dose pharmacokinetics of diazepam following once-daily administration of a controlled-release capsule.

    abstract::The study was designed to determine the steady-state pharmacokinetic profile of diazepam and desmethyldiazepam following a 15-mg controlled-release capsule dosed once daily at either 7 a.m. or 11 p.m. compared with the respective profiles of the conventional 5-mg tablet dosed three times a day at 7 a.m., 12 p.m., and ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/00007691-198312000-00008

    authors: Wills RJ,Colburn WA

    更新日期:1983-01-01 00:00:00

  • Effect of antacids on phenytoin bioavailability.

    abstract::Eight subjects were studied in a randomized crossover design to determine the effect of aluminum-magnesium hydroxide (AMH), calcium carbonate (CC), and aluminum hydroxide-magnesium trisilicate (AHMT) on the bioavailability of a single, 600-mg dose of phenytoin administered orally. Each subject received phenytoin alone...

    journal_title:Therapeutic drug monitoring

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00007691-198104000-00003

    authors: Carter BL,Garnett WR,Pellock JM,Stratton MA,Howell JR

    更新日期:1981-01-01 00:00:00

  • Analytical Validation and Cross-Validation of an NFAT-Regulated Gene Expression Assay for Pharmacodynamic Monitoring of Therapy With Calcineurin Inhibitors.

    abstract:BACKGROUND:Analysis of residual gene expression of the nuclear factor of activated T cell (NFAT)-regulated genes has been developed as a pharmacodynamic biomarker to monitor therapy with calcineurin inhibitors. The availability of commercial primer sets (Search-LC) and the well-established assay protocol makes this bio...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章

    doi:10.1097/FTD.0000000000000340

    authors: Abdel-Kahaar E,Giese T,Sommerer C,Rieger H,Shipkova M,Wieland E

    更新日期:2016-12-01 00:00:00

  • Valproate monotherapy in juvenile myoclonic epilepsy: dose-related effects on electroencephalographic and other neurophysiologic tests.

    abstract::A neurophysiologic test battery (consisting of a 24-hour, seven-channel electroencephalogram [EEG], EEG spectral analysis, multiple sleep latency test, visual evoked potentials, critical flicker fusion, and visual contrast sensitivity) was administered twice to 16 patients with juvenile myoclonic epilepsy (JME) in a d...

    journal_title:Therapeutic drug monitoring

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00007691-199902000-00014

    authors: Sundqvist A,Nilsson BY,Tomson T

    更新日期:1999-02-01 00:00:00