scholarly journals Therapeutic Drug Monitoring of Antiepileptic Drugs in Real Clinical Practice in Russia

2018 ◽  
Vol 3 (5) ◽  
Keyword(s):  
Clinical Practice ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
High Performance ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Average Dose ◽  
Observation Study ◽  
Daily Dose ◽  
Real Clinical Practice

Introduction: Anticonvulsants refer to drugs with interindividual variability of plasma concentrations and clinical efficacy. Therapeutic drug monitoring (TDM) is an important tool for optimizing pharmacotherapy with anticonvulsants in real clinical practice. The aim of the study was to analyze the results of TDM of valproates (VPA) and carbamazepine (CBZ) in epilepsy adults in clinical practice in Russia. Methods: observation study in 800 epilepsy adults (mean age 35.5±0.5) the rate of achievement the therapeutic concentrations (TC) of VPA and CBZ in different drug forms using high performance liquid chromatography; range of TC for VPA 50-150 mg/l, for CBZ 4-12 mg/l. Results: The frequency of achievement TC on VPA was 66.4% in average dose – 1325.1±29.6 mg/day with no difference between sustain-released and immediate-released drug forms. Gender differences of VPA concentrations were identified: women mean Cmin and Cmax were higher than in men with significantly lower daily dose. The frequency of sub-TC VPA was 16.3% and over-TC – 1% (Cmax 164.2±2.4mg/l); the toxic concentration for CNS (175 mg/l) was not achieved. In VPA doses<500mg/day there was no patients with TC; in 1001–1500 mg/day TC have 75%, in doses 1501–2000mg/day – 97%; in >2000 mg/day – 86% and there was high risk of over-TC (4%). The frequency of achievement TC range VPA monotherapy was 2 times more than in combination VPA+CBZ (67% versus 34%). The frequency of achievement TC range on CBZ was 78.6%, the average daily dose was 922.2±23.0 mg/day with significantly higher rate of TC range achievement when using sustain-release forms of CBZ. The frequency of sub-TC CBZ was 6.3%, over-TC – 1.25%. In patients with over-TC mean dose was 1250 mg/day, Cmin 13.5±0.2mg/l, Cmax 15.1±0.7mg/l. At initial doses<600 mg/day 64.3% patients have TC; in doses>600 mg/day – 87%. In daily doses 600-1200 mg and >1200 mg 1.3% and 4.1% patients have over-TC by both Cmin and Cmax, only by Cmax – 8.8% and 18.4%, respectively. Conclusion: the frequency of TC on VPA and CBZ is high with rare cases of over-TC, but there was problem of paradox low concentrations in single cases. CBZ have less predictable concentrations in therapeutic doses range than VPA.

scholarly journals Therapeutic drug monitoring of levetiracetam in daily clinical practice: high-performance liquid chromatography versus immunoassay

2018 ◽  
Vol 27 (e1) ◽  
pp. e2-e6 ◽  
Author(s):  
Maria Mendoza Aguilera ◽  
María Dolores Bellés Medall ◽  
Tamara Álvarez Martín ◽  
Óscar Pascual Marmaneu ◽  
Carla Liñana Granell ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Clinical Practice ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
High Performance ◽  
Daily Clinical Practice ◽  
Therapeutic Drug

Therapeutic drug monitoring of nivolumab in clinical practice: Preliminary experience.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14089-e14089
Author(s):  
Manuel Sureda ◽  
Ana Catalán-Latorre ◽  
Juan José Mata ◽  
Vanesa Escudero ◽  
Antonio Brugarolas
Keyword(s):  
Clinical Practice ◽  
Steady State ◽  
Therapeutic Drug Monitoring ◽  
Solid Tumors ◽  
Drug Monitoring ◽  
Cell Cancer ◽  
Plasma Concentrations ◽  
Fixed Dose ◽  
Therapeutic Drug ◽  
Multiple Tumor

e14089 Background: Fixed dose schemes, regardless of body weight, have been accepted by the regulatory agencies for the PD-1 targeting antibodies. Zaho X. and Ratain M. have elucidated that the mean steady state concentrations of nivolumab (N) at flat-doses of 240 mg Q2W or 480 mg Q4W were 57 µg/mL and 47 µg/mL, respectively. These levels are very similar to those observed at the dosage of 3 mg/kg Q2W. Considering the long half-life of N, its mechanism of action and the absence of correlation between exposure and response or toxicity at clinically tested doses, other schemes can be explored. Moreover, therapeutic drug monitoring (TDM) can contribute to individualize and optimize dosage. We determined serum N levels in patients with solid tumors. Methods: The PK profile of N was analyzed in 15 patients with solid tumors who received 3 mg/kg Q2W from May 2017 through January 2019. Eligible patients had non-small-cell lung cancer (n = 7), urothelial cancer (n = 1), gastric cancer (n = 1), breast cancer (n = 1), renal cell cancer (n = 1), colorectal cancer (n = 1), prostate cancer (n = 1), melanoma (n = 1) and sarcoma (n = 1). Free N serum concentrations were determined with a quantitative ELISA capable of detecting ≥ 0.3 µg/mL (Shikari Q-Nivo, Matriks Biotek, Ankara, Turkey). A total of 28 TDM were done after steady state (6th and 26th cycle). Results: For different reasons, 9 patients received N at 3, 4, 5, 6 or 7 week intervals once the steady state was reached. In these patients, a median reduction of 20.8% (6.7% - 43.0%) of the received doses was observed. Mean plasma concentrations of N observed after administration every 2 weeks was 73.5±32.5 µg/mL (n = 9). Once the steady state was reached, mean plasma concentrations at 3, 4, 5, 6 or 7 weeks, were 54.0±1.3 µg/mL (n = 2), 45.1±25.3 µg/mL (n = 7), 42.9±29.5 µg/mL (n = 5) and 24.4±11.7 µg/mL (n = 5), respectively. No statistically significant differences were observed in the serum levels of N between the dosing intervals of 3, 4 and 5 weeks and the standard regimen (Q2W) (p > 0.05). These data are similar to those described by Long G.V. et al. that compared N pharmacokinetic exposure for the 480 mg Q4W schedule simulated in 3817 patients across multiple tumor types with those for the 3 mg/kg Q2W and 240 mg Q2W schedules. Conclusions: The incorporation of the TDM of N in routine clinical practice could help to maintain a therapeutic drug plasma concentration with lower or less frequent doses, adding a financial benefit, without decreasing clinical efficacy. Further randomized trials to explore alternative dosing schemes of N, including personalization through TDM, are warranted

Determination of Imatinib Plasma Levels by High Performance Liquid Chromatography (HPLC): Evaluation of Pharmacokinetic Variability and Haematological Consequences.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1375-1375 ◽  
Author(s):  
Stephanie Haiat ◽  
Xavier Decleves ◽  
Benedicte Mittaine ◽  
Ollivier Legrand ◽  
Stephanie Francart ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Plasma Concentrations ◽  
Cytogenetic Response ◽  
Therapeutic Drug ◽  
Large Variability ◽  
Complete Cytogenetic Response ◽  
Daily Dose ◽  
Trough Levels

Abstract Imatinib exerts a potent and selective inhibition of tyrosine kinase Bcr-Abl. It is currently used for treatment of chronic myeloid leukaemia (CML) and acute leukaemia (AL). Pharmacokinetic data indicate large variability especially in plasma exposure with many factors which could be involved (absorption, metabolism, drug-drug interactions). Compliance must also be taken in count. The aim of this study was to determine the variability of imatinib plasma concentrations in a « natural clinical setting» (outpatients on long-term treatment for CML or AL). Secondary objective was to perform a pilot assessment of the relationship between imatinib plasma concentration and clinical outcomes. Analysis was performed by HPLC. Sample treatment (500 μL of patient plasma) consisted of a liquid-solid extraction. Imatinib and internal standard (CGP 53716) were eluted on a Lichrosorb® RP8 column with methanol-THF-sodium acetate buffer 0.1M pH 5. Detection was performed with UV spectrophotometer (262 nm). The limit of quantification was set at 200 ng/mL. Within-day and inter-day precisions were lower than 15%. Blood samples were collected at steady-state (trough and peak values, ie before and 3h after drug administration) in outpatients treated for CML or AL with one imatinib daily dose, at clinical visits. Clinical evolution was considered as successful when following responses were obtained: complete haematological response within 3 months, or major cytogenetic response within 6 months, or complete cytogenetic response within 12 months, or major molecular response within 18 months in the CML group, and complete cytogenetic response after induction in the AL group. 68 imatinib measurements were obtained from 24 patients (13 CML and 11 AL). Mean age was 49 years (range 21–74) and weight was 73 kg (49–100). In patients receiving imatinib 400mg daily dose, trough and peak concentrations were respectively 1.60 ±1.28 (0.5–5.1) μg/mL (n=19), and 3.51 ±3.04 (1.0–11.1) μg/mL (n=9). In patients treated with a daily dose 600mg, trough and peak concentrations were respectively 2.62 ±2.10 (0.8–6.5) μg/mL (n=22), and 5.85 ±4.15 (1.2–15.1) μg/mL (n=18). Variability of trough concentrations of imatinib were 80% in both groups (400 and 600mg). 18 patients were evaluable. 15 efficient responses were obtained and all these patients showed imatinib trough levels above 0.5 μg/mL (target plasma concentration required to induce death of leukaemic cells). 3 patients with failure showed nevertheless imatinib trough levels of 1.5, 1.8 and 4.5 μg/mL. 3 patients showed accumulation of imatinib (trough levels higher than 5.0 μg/mL) due to hepatic impairment but without side effects. The method of analysis is very simple, sensitive and specific. Our results confirm the large variability of imatinib plasma concentrations and are consistent with previous results. These preliminary results showed a « safe » imatinib exposure which leads to therapeutic concentrations (higher than 0.5 μg/mL). Therapeutic drug monitoring seems to be not systematicaly necessary but could be reserved to specific cases of poor compliance, major risks of interaction or cases of failure or resistance. Studies of correlation with a larger cohort of patients is necessary to clarify the role of imatinib therapeutic drug monitoring for improving its use.

scholarly journals Therapeutic Drug Monitoring of Linezolid: a Retrospective Monocentric Analysis

2010 ◽  
Vol 54 (11) ◽  
pp. 4605-4610 ◽  
Author(s):  
Federico Pea ◽  
Mario Furlanut ◽  
Piergiorgio Cojutti ◽  
Francesco Cristini ◽  
Eleonora Zamparini ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
High Performance ◽  
Drug Exposure ◽  
Plasma Concentrations ◽  
Hplc Method ◽  
Therapeutic Drug ◽  
Time Curve ◽  
Standard Dosage ◽  
Wide Variability

ABSTRACT The objective of the present retrospective observational study carried out in patients receiving a standard dosage of linezolid and undergoing routine therapeutic drug monitoring (TDM) was to assess the interindividual variability in plasma exposure, to identify the prevalence of attainment of optimal pharmacodynamics, and to define if an intensive program of TDM may be warranted in some categories of patients. Linezolid plasma concentrations (trough [C min] and peak [C max] levels) were analyzed by means of a high-performance liquid chromatography (HPLC) method, and daily drug exposure was estimated (daily area under the plasma concentration-time curve [AUC24]). The final database included 280 C min and 223 C max measurements performed in 92 patients who were treated with the fixed 600-mg dose every 12 h (q12h) intravenously (n = 58) or orally (n = 34). A wide variability was observed (median values [interquartile range]: 3.80 mg/liter [1.75 to 7.53 mg/liter] for C min, 14.70 mg/liter [10.57 to 19.64] for C max, and 196.08 mg·h/liter [144.02 to 312.10 mg·h/liter] for estimated AUC24). Linezolid C min was linearly correlated with estimated AUC24 (r 2 = 0.85). Optimal pharmacodynamic target attainment (defined as C min of ≥2 mg/liter and/or AUC24/MIC90 ratio of >80) was obtained in about 60 to 70% of cases, but potential overexposure (defined as C min of ≥10 mg/liter and/or AUC24 of ≥400 mg·h/liter) was documented in about 12% of cases. A significantly higher proportion of cases with potential overexposure received cotreatment with omeprazole, amiodarone, or amlodipine. Our study suggests that the application of TDM might be especially worthwhile in about 30% of cases with the intent of avoiding either the risk of dose-dependent toxicity or that of treatment failure.

scholarly journals Isavuconazole Concentration in Real-World Practice: Consistency with Results from Clinical Trials

2018 ◽  
Vol 62 (7) ◽  
Author(s):  
David Andes ◽  
Laura Kovanda ◽  
A. Desai ◽  
Therese Kitt ◽  
M. Zhao ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Therapeutic Drug Monitoring ◽  
Real World ◽  
Drug Monitoring ◽  
Antifungal Agents ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Clinical Use

ABSTRACT Clinical use of voriconazole, posaconazole, and itraconazole revealed the need for therapeutic drug monitoring (TDM) of plasma concentrations of these antifungal agents. This need for TDM was not evident from clinical trials. In order to establish whether this requirement also applies to isavuconazole, we examined the plasma concentrations of 283 samples from patients receiving isavuconazole in clinical practice and compared the values with those from clinical trials. The concentration distributions from real-world use and clinical trials were nearly identical (>1 μg/ml in 90% of patients). These findings suggest that routine TDM may not be necessary for isavuconazole in most instances.

scholarly journals Impact on Antibiotic Resistance, Therapeutic Success, and Control of Side Effects in Therapeutic Drug Monitoring (TDM) of Daptomycin: A Scoping Review

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 263
Author(s):  
Carolina Osorio ◽  
Laura Garzón ◽  
Diego Jaimes ◽  
Edwin Silva ◽  
Rosa-Helena Bustos
Keyword(s):  
Side Effects ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Bacterial Resistance ◽  
Plasma Concentrations ◽  
Resistant Bacteria ◽  
Therapeutic Drug ◽  
Therapeutic Success ◽  
Favorable Clinical Outcome ◽  
And Control

Antimicrobial resistance (AR) is a problem that threatens the search for adequate safe and effective antibiotic therapy against multi-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE) and Clostridium difficile, among others. Daptomycin is the treatment of choice for some infections caused by Gram-positive bacteria, indicated most of the time in patients with special clinical conditions where its high pharmacokinetic variability (PK) does not allow adequate plasma concentrations to be reached. The objective of this review is to describe the data available about the type of therapeutic drug monitoring (TDM) method used and described so far in hospitalized patients with daptomycin and to describe its impact on therapeutic success, suppression of bacterial resistance, and control of side effects. The need to create worldwide strategies for the appropriate use of antibiotics is clear, and one of these is the performance of therapeutic drug monitoring (TDM). TDM helps to achieve a dose adjustment and obtain a favorable clinical outcome for patients by measuring plasma concentrations of an administered drug, making a rational interpretation guided by a predefined concentration range, and, thus, adjusting dosages individually.

scholarly journals Rapid point-of-care anti-infliximab antibodies detection in clinical practice: comparison with ELISA and potential for improving therapeutic drug monitoring in IBD patients

2021 ◽  
Vol 14 ◽  
pp. 175628482199990
Author(s):  
Sonia Facchin ◽  
Andrea Buda ◽  
Romilda Cardin ◽  
Nada Agbariah ◽  
Fabiana Zingone ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Point Of Care ◽  
Drug Clearance ◽  
Elisa Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Drug ◽  
Drug Concentrations ◽  
Inflammatory Bowel

Anti-drug antibodies can interfere with the activity of anti-tumor necrosis factor (TNF) agents by increasing drug clearance via direct neutralization. The presence of anti-drug antibodies is clinically relevant when trough drug concentrations are undetectable or sub-therapeutic. However, traditional immunoassay is not easily and rapidly accessible, making the translation of the results into treatment adjustment difficult. The availability of a point-of-care (POC) test for therapeutic drug monitoring (TDM) might represent an important step forward for improving the management of inflammatory bowel disease (IBD) patients in clinical practice. In this pilot study, we compared the results obtained with POC tests with those obtained by enzyme-linked immunosorbent assay (ELISA) in a group of IBD patients treated with Infliximab (IFX). We showed that POC test can reliably detect presence of antibody-to-IFX with 100% of specificity and 76% sensitivity, in strong agreement with the ELISA test ( k-coefficient = 0.84).

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