Therapeutic Drug Monitoring in Buprenorphine/Naloxone Treatment for Opioid Use Disorder: Clinical Feasibility and Optimizing Assay Precision

2020 ◽  
Vol 53 (03) ◽  
pp. 115-121
Author(s):  
Hesham Farouk Elarabi ◽  
Nael Hasan ◽  
John Marsden ◽  
Doaa Radwan ◽  
Abdu Adem ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Maintenance Treatment ◽  
Limit Of Detection ◽  
Opioid Use Disorder ◽  
Therapeutic Drug ◽  
Opioid Use ◽  
Limit Of Quantitation ◽  
Trough Concentrations ◽  
Assay Precision

Abstract Introduction Compliance with sublingual buprenorphine/naloxone (SL-BUP/NX) is associated with higher abstinence from illicit opioid use. Therapeutic drug monitoring (TDM) has been recommended for adherence monitoring of buprenorphine (BUP) maintenance treatment for opioid use disorder (OUD), but to date there have been no reported clinical applications. In this TDM feasibility study, we investigated BUP assay precision in 15 adults with OUD who had been stabilized on buprenorphine/naloxone. Methods Using solid phase extraction, BUP recovery was contrasted at 100 mMol and 1 Molar of acetic acid wash solution. Precision was determined by applying the condition generating highest recovery using 0.2 ng/mL and 10 ng/mL standards. Four blood samples were drawn to examine the BUP peak and trough plasma concentrations, and BUP elimination rate was estimated. BUP recovery was examined again in a random sample and contrasted with the concentration predicted applying first-order kinetics. Results Higher BUP recovery was achieved with 1 Molar wash (94.3%; p=0.05). Precision ranged from 15–20%. The estimated limit of detection (LoD) and limit of quantitation (LoQ) were 0.02 and 0.069 ng/mL, respectively. BUP peak and trough concentrations were successfully examined, and BUP trough concentrations were replicated confirming steady state. BUP concentrations were predicted at a variance of −7.20% to 1.54 %. Conclusions TDM for BUP maintenance treatment of OUD is feasible, and simple adjustment of the assay conditions enhances BUP recovery.

scholarly journals PERFORMANCE CHARACTERISTICS OF A FRET-BASED IMMUNOASSAY FOR QUANTITATION OF INFLIXIMAB ON A POINT-OF-CARE INSTRUMENT SYSTEM

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S57-S57
Author(s):  
Edgar Ong ◽  
Ruo Huang ◽  
Richard Kirkland ◽  
Michael Hale ◽  
Larry Mimms
Keyword(s):  
Whole Blood ◽  
Limit Of Detection ◽  
Point Of Care ◽  
Quantitative Detection ◽  
Therapeutic Drug ◽  
Analytical Sensitivity ◽  
Sample Type ◽  
Hook Effect ◽  
Limit Of Quantitation ◽  
Assay Precision

Abstract Introduction A fast (<5 min), time-resolved fluorescence resonance energy transfer (FRET)-based immunoassay was developed for the quantitative detection of infliximab (IFX) and biosimilars for use in therapeutic drug monitoring using only 20 µL of fingerstick whole blood or serum at the point-of-care. The Procise IFX assay and ProciseDx analyzer are CE-marked. Studies were performed to characterize analytical performance of the Procise IFX assay on the ProciseDx analyzer. Methods Analytical testing was performed by spiking known amounts of IFX into negative serum and whole blood specimens. Analytical sensitivity was determined using limiting concentrations of IFX. Linearity was determined by testing IFX across the assay range. Hook effect was assessed at IFX concentrations beyond levels expected to be found within a patient. Testing of assay precision, cross-reactivity and potential interfering substances, and biosimilars was performed. The Procise IFX assay was also compared head-to-head with another CE-marked assay: LISA-TRACKER infliximab ELISA test (Theradiag, France). The accuracy of the Procise IFX assay is established through calibrators and controls traceable to the WHO 1st International Standard for Infliximab (NIBSC code: 16/170). Results The Procise IFX assay shows a Limit of Blank, Limit of Detection, and Lower Limit of Quantitation (LLoQ) of 0.1, 0.2, and 1.1 µg/mL in serum and 0.6, 1.1, and 1.7 µg/mL in whole blood, respectively. The linear assay range was determined to be 1.7 to 77.2 µg/mL in serum and whole blood. No hook effect was observed at an IFX concentration of 200 µg/mL as the value reported as “>ULoQ”. Assay precision testing across 20 days with multiple runs and reagent lots showed an intra-assay coefficient of variation (CV) of 2.7%, an inter-assay CV of <2%, and a total CV of 3.4%. The presence of potentially interfering/cross-reacting substances showed minimal impact on assay specificity with %bias within ±8% of control. Testing of biosimilars (infliximab-dyyb and infliximab-abda) showed good recovery. A good correlation to the Theradiag infliximab ELISA was obtained for both serum (slope=1.01; r=0.99) and whole blood (slope=1.01; r=0.98) samples (Figure 1). Conclusion Results indicate that the Procise IFX assay is sensitive, specific, and precise yielding results within 5 minutes from both whole blood and serum without the operator needing to specify sample type. Additionally, it shows very good correlation to a comparator assay that takes several hours and sample manipulation to yield results. This makes the Procise IFX assay ideal for obtaining fast and accurate IFX quantitation, thus allowing for immediate drug level dosing decisions to be made by the physician during patient treatment.

Intra-individual variability in lopinavir plasma trough concentrations supports therapeutic drug monitoring

AIDS ◽  
2003 ◽  
Vol 17 (7) ◽  
pp. 1107-1108 ◽  
Author(s):  
Marta Boffito ◽  
David J Back ◽  
Patrick G Hoggard ◽  
Annamaria Caci ◽  
Stefano Bonora ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Individual Variability ◽  
Therapeutic Drug ◽  
Trough Concentrations

scholarly journals Therapeutic Drug Monitoring of Voriconazole in Children from a Tertiary Care Center in China

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
Lin Hu ◽  
Ting-ting Dai ◽  
Le Zou ◽  
Tao-ming Li ◽  
Xuan-sheng Ding ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Care Center ◽  
Tertiary Care ◽  
Target Range ◽  
Therapeutic Drug ◽  
Affecting Factors ◽  
Administration Routes ◽  
Asian Children ◽  
Trough Concentrations

ABSTRACT Voriconazole is a broad-spectrum triazole antifungal and the first-line treatment for invasive aspergillosis (IA). The aim of this research was to study the dose adjustments of voriconazole as well as the affecting factors influencing voriconazole trough concentrations in Asian children to optimize its daily administration. Clinical data were analyzed of inpatients 2 to 14 years old who were subjected to voriconazole trough concentration monitoring from 1 June 2015 to 1 December 2017. A total of 138 voriconazole trough concentrations from 42 pediatric patients were included. Voriconazole trough concentrations at steady state ranged from 0.02 to 9.35 mg/liter, with high inter- and intraindividual variability. Only 50.0% of children achieved the target range (1.0 to 5.5 mg/liter) at initial dosing, while 35.7% of children were subtherapeutic, and 14.3% of children were supratherapeutic at initial dosing. There was no correlation between initial trough concentrations and initial dosing. A total of 28.6% of children (12/42) received an adjusted dose according to trough concentrations. Children <6, 6 to 12, and >12 years old required a median oral maintenance dose to achieve the target range of 11.1, 7.2, and 5.3 mg/kg twice daily, respectively (P = 0.043). The average doses required to achieved the target range were 7.7 mg/kg and 5.6 mg/kg, respectively, and were lower than the recommended dosage (P = 0.033 and 0.003, respectively). Affecting factors such as administration routes and coadministration with proton pump inhibitors (PPIs) explained 55.3% of the variability in voriconazole exposure. Therapeutic drug monitoring (TDM) of voriconazole could help to individualize antifungal therapy for children and provide guidelines for TDM and dosing optimization in Asian children.

scholarly journals Use of Therapeutic Drug Monitoring to Characterize Cefepime-Induced Neurotoxicity

2020 ◽  
Author(s):  
Veena Venugopalan ◽  
Cara Nys ◽  
Natalie Hurst ◽  
Yiqing Chen ◽  
Maria Bruzzone ◽  
...  
Keyword(s):  
Renal Function ◽  
Therapeutic Drug Monitoring ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Hospitalized Patients ◽  
Therapeutic Drug ◽  
Eeg Abnormalities ◽  
Increased Risk ◽  
Trough Concentrations ◽  
The Relationship

AbstractBackgroundThe incidence of cefepime-induced neurotoxicity (CIN) in hospitalized patients is highly variable. Although greater cefepime exposures incite neurotoxicity, data evaluating trough thresholds associated with CIN remains limited. The objectives of this study were to evaluate the incidence of CIN, assess the relationship between cefepime trough concentrations and CIN, investigate clinical factors associated with CIN, and describe electroencephalogram (EEG) abnormalities in CIN.MethodsThis was a retrospective study of adult patients who had received ≥ 5 days of cefepime with ≥ 1 trough concentration > 25 mg/L. Potential CIN cases were identified utilizing neurological symptoms, neurologist assessments, EEG findings and improvement of neurotoxicity after cefepime discontinuation.ResultsOne-hundred and forty-two patients were included. The incidence of CIN was 13% (18/142). The mean cefepime trough concentration in CIN patients was significantly greater than the non-neurotoxicity group (74.2 mg/L ± 41.1 vs. 46.6 mg/L ± 23, p=0.015). Lower renal function (creatinine clearance < 30 ml/min), greater time to therapeutic drug monitoring (TDM) (≥72 hours), and each 1 mg/mL rise in cefepime trough were independently associated with increased risk of CIN. Moderate generalized slowing of the background rhythm was the most common EEG pattern associated with CIN.ConclusionCefepime should be used cautiously in hospitalized patients due to the risk of neurotoxicity. Patients with greater renal function and those who had early cefepime TDM (≤ 72 hours) had lower risk of CIN.

An UHPLC-UV Method for Determination of Vancomycin in human serum

2020 ◽  
Vol 16 ◽  
Author(s):  
Fang Fang ◽  
Ning Li ◽  
Chunli Xu ◽  
Rong Tan ◽  
Jihong Yang ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Human Serum ◽  
Drug Monitoring ◽  
Internal Standard ◽  
Sample Pretreatment ◽  
Gradient Elution ◽  
Therapeutic Drug ◽  
Serum Samples ◽  
Column Temperature ◽  
Limit Of Quantitation

Objective: To develop a rapid ultra-performance liquid chromatographic (UHPLC)-UV method for vancomycin determination in human serum for therapeutic drug monitoring (TDM). Methods: Human serum samples were precipitated with 10% perchloric acid, and the supernatant after centrifugation was analyzed on an ACQUITY UHPLC BEH C18 column (2.1 × 50mm, 1.7 μm) via gradient elution with a flow rate at 0.3 mL/min. The mobile phase consisted of acetonitrile and 0.005M KH2PO4 buffer (containing 0.1% triethylamine, pH 3.4). The detection wavelength was set at 210 nm, and the column temperature was set at 40. The total runtime was 6.0 min per analysis. Results: After comprehensive validation, the method was applied to determine the concentration of vancomycin in human serum. The chromatographic peaks of vancomycin and internal standard were not interfered by endogenous matrixes. The retention time (RT) of vancomycin was 1.91 min, while the internal standard was 1.58 min. The good linearity range of vancomycin concentration was 2.5-120 μg/mL (R2>0.999). The lower limit of quantitation (LLOQ) was 2.5 μg/mL. The precision at three quality control (QC) levels (including LLOQ) was restricted within 85-115%. The extraction recovery rate of QC samples (4.0, 20.0, 60.0 μg/mL) were 101.16%、97.70%、94.90%, respectively. Inter- and intra-day precision was less than 8% (RSD). Stability tests under different storage conditions were satisfactory. In patients, the concentration of vancomycin ranged from 7.30 to 89.12 μg/mL determined by the fully validated method. Conclusion: The simple, rapid sample pretreatment procedures and short analysis time made this UHPLC-UV method suitable for therapeutic drug monitoring (TDM) of vancomycin.

scholarly journals Raman spectroscopy as a potential tool for label free therapeutic drug monitoring in human serum: the case of busulfan and methotrexate

The Analyst ◽  
2019 ◽  
Vol 144 (17) ◽  
pp. 5207-5214 ◽  
Author(s):  
Drishya Rajan Parachalil ◽  
Deirdre Commerford ◽  
Franck Bonnier ◽  
Igor Chourpa ◽  
Jennifer McIntyre ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Multivariate Analysis ◽  
Therapeutic Drug Monitoring ◽  
Human Serum ◽  
Drug Monitoring ◽  
Limit Of Detection ◽  
Therapeutic Drug ◽  
Label Free ◽  
Limit Of Quantification ◽  
Potential Tool

A methodology is proposed, based on Raman spectroscopy coupled with multivariate analysis, to determine the Limit of Detection (LOD) and Limit of Quantification (LOQ) for therapeutic drug monitoring in human serum, using the examples of Busulfan and Methotrexate.

scholarly journals Therapeutic drug monitoring of once daily tobramycin in cystic fibrosis—caution with trough concentrations

2007 ◽  
Vol 6 (2) ◽  
pp. 125-130 ◽  
Author(s):  
Kingsley P. Coulthard ◽  
Daniel G. Peckham ◽  
Steven P. Conway ◽  
Carol A. Smith ◽  
Jan Bell ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Once Daily ◽  
Trough Concentrations
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