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  1. Article ; Online: Continuous infusion of cefiderocol in a critically ill patient with continuous venovenous haemofiltration.

    Möhlmann, Julia E / van Luin, Matthijs / Uijtendaal, Esther V / Zahr, Noël / Sikma, Maaike A

    British journal of clinical pharmacology

    2023  Volume 89, Issue 12, Page(s) 3753–3757

    Abstract: Cefiderocol is a broad-spectrum cephalosporin antibiotic and is indicated in patients with difficult-to-treat Gram-negative bacterial infections. Cefiderocol is applied as a 2-4-times daily prolonged 3-h infusion. The therapeutic target of cefiderocol ... ...

    Abstract Cefiderocol is a broad-spectrum cephalosporin antibiotic and is indicated in patients with difficult-to-treat Gram-negative bacterial infections. Cefiderocol is applied as a 2-4-times daily prolonged 3-h infusion. The therapeutic target of cefiderocol suggests that continuous infusion (CI) may be advantageous, since it is more likely to achieve 100% of time of the unbound concentration above the minimal inhibitory concentration (MIC). However, limited information on cefiderocol as CI has been assessed. We present a case of a critically ill 37-year-old woman with continuous venovenous haemofiltration (CVVH) treated with a CI of cefiderocol for multidrug-resistant Pseudomonas aeruginosa. She received 4 g per 24 h, in accordance with the recommendations for the total daily dose during CVVH with an effluent flow rate of 2.1-3 L/h. We evaluated intraperitoneal, plasma arterial pre- and postfilter and ultrafiltrate (urine) total cefiderocol concentrations and discussed the pharmacokinetics in respect to the CVVH settings. The predicted unbound plasma concentrations during CI resulted in 6.8-9.5-fold higher concentrations than the adopted MIC of 2 mg/L for cefiderocol against P. aeruginosa. The optimal time of the unbound concentration >MIC target of cefiderocol was met during the sampling period, suggesting adequate exposure during the total treatment period. The obtained intraperitoneal concentration indicated adequate cefiderocol exposure at the site of infection. Continuous infusion of 4 g cefiderocol per 24 h led to sufficient plasma concentrations in our anuric critically ill patient treated with CVVH. This case is supportive to the use of cefiderocol as continuous infusion.
    MeSH term(s) Female ; Humans ; Adult ; Anti-Bacterial Agents ; Critical Illness/therapy ; Continuous Renal Replacement Therapy ; Cephalosporins/pharmacokinetics ; Cefiderocol
    Chemical Substances Anti-Bacterial Agents ; Cephalosporins
    Language English
    Publishing date 2023-09-20
    Publishing country England
    Document type Case Reports
    ZDB-ID 188974-6
    ISSN 1365-2125 ; 0306-5251 ; 0264-3774
    ISSN (online) 1365-2125
    ISSN 0306-5251 ; 0264-3774
    DOI 10.1111/bcp.15901
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Interlaboratory comparison study of immunosuppressant analysis using a fully automated LC-MS/MS system.

    Zahr, Noël / Duce, Helen / Duffy, Joanne / Webster, Craig / Rentsch, Katharina M

    Clinical chemistry and laboratory medicine

    2022  Volume 60, Issue 11, Page(s) 1753–1762

    Abstract: Objectives: All guidelines recommend LC-MS/MS as the analytical method of choice for the quantification of immunosuppressants in whole blood. Until now, the lack of harmonization of methods and the complexity of the analytical technique have prevented ... ...

    Abstract Objectives: All guidelines recommend LC-MS/MS as the analytical method of choice for the quantification of immunosuppressants in whole blood. Until now, the lack of harmonization of methods and the complexity of the analytical technique have prevented its widespread use in clinical laboratories. This can be seen in international proficiency schemes, where more than half of the participants used immunoassays. With the Cascadion SM Clinical analyzer (Thermo Fisher Scientific, Oy, Vantaa, FI) a fully automated LC-MS/MS system has been introduced, which enables the use of LC-MS/MS without being an expert in mass spectrometry.
    Methods: To verify the interlaboratory comparison of the immunosuppressant assay on this type of instrument, three centers across Europe compared 1097 routine whole blood samples, each site sharing its own samples with the other two. In other experiments, the effects of freezing and thawing of whole blood samples was studied, and the use of secondary cups instead of primary tubes was assessed.
    Results: In the Bland-Altman plot, the comparison of the results of tacrolimus in fresh and frozen samples had an average bias of only 0.36%. The respective data for the comparison between the primary and secondary tubes had an average bias of 1.14%. The correlation coefficients for patient samples with cyclosporine A (n=411), everolimus (n=139), sirolimus (n=114) and tacrolimus (n=433) were 0.993, 0.993, 0.993 and 0.990, respectively.
    Conclusions: The outcome of this study demonstrates a new level of result harmonization for LC-MS/MS based immunosuppressant analysis with a commercially available fully automated platform for routine clinical application.
    MeSH term(s) Chromatography, Liquid/methods ; Cyclosporine ; Drug Monitoring/methods ; Everolimus ; Humans ; Immunosuppressive Agents ; Sirolimus ; Tacrolimus ; Tandem Mass Spectrometry/methods
    Chemical Substances Immunosuppressive Agents ; Cyclosporine (83HN0GTJ6D) ; Everolimus (9HW64Q8G6G) ; Sirolimus (W36ZG6FT64) ; Tacrolimus (WM0HAQ4WNM)
    Language English
    Publishing date 2022-09-02
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1418007-8
    ISSN 1437-4331 ; 1434-6621 ; 1437-8523
    ISSN (online) 1437-4331
    ISSN 1434-6621 ; 1437-8523
    DOI 10.1515/cclm-2021-1340
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Management of cancer treatments in hemodialysis patients.

    Matte, Paul / Bihan, Kevin / Isnard-Bagnis, Corinne / Zahr, Noël / Thiery-Vuillemin, Antoine / Gougis, Paul / Campedel, Luca

    Bulletin du cancer

    2023  

    Abstract: Introduction: The number of cancer patients receiving long-term hemodialysis (HD) is increasing, and HD could jeopardize treatments' safety and efficacy. Therefore, managing anticancer drugs is critical in this frail population. In addition, evidence of ...

    Abstract Introduction: The number of cancer patients receiving long-term hemodialysis (HD) is increasing, and HD could jeopardize treatments' safety and efficacy. Therefore, managing anticancer drugs is critical in this frail population. In addition, evidence of HD safety or risk is regularly released both for cytotoxic chemotherapy (CT) or hormone therapy (HT) as well as new therapies with molecularly targeted therapies (MTT), immune checkpoint inhibitors (ICI), and a summary of current knowledge is needed.
    Methods: We aimed to synthesize available data on cancer treatments in HD patients using PubMed database, FDA labels, summary of product characteristics (SmPC), FDA and EMA approval documents, guidelines and finally case reports for which relevant pharmacokinetic (PK) data is available.
    Results: For CT, recently proposed guidelines were balanced by the publication of particular toxic reports following them. SmPC was helpful in some cases, but no data was found for most CTs. MTT, both oral and monoclonal antibodies, were rarely modified by HD. However, HD patients have particular frailty that could require dose adaptation despite no substantial PK modification. Similarly, exposure to ICIs is unlikely to be modified by HD since immunoglobulins are not dialyzable. For HT, PK characteristics and HD impact were more heterogeneous and were reviewed molecule by molecule.
    Conclusions: We summarized current knowledge on HD and cancer treatments. Data remains scarce, and the latest guidelines rely on few clinical data. There is a need to collect both retrospective and prospective data to better characterize the safety and relevant dose and schedule adaptations whenever needed in this situation to reinforce future guidelines.
    Language English
    Publishing date 2023-03-15
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 213270-9
    ISSN 1769-6917 ; 0007-4551
    ISSN (online) 1769-6917
    ISSN 0007-4551
    DOI 10.1016/j.bulcan.2023.01.018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Low plasma belimumab levels as an indicator of poor adherence to belimumab in patients with systemic lupus erythematosus.

    Trefond, Ludovic / Zahr, Noël / Lhote, Raphael / Pha, Micheline / Hié, Miguel / Miyara, Makoto / Papo, Matthias / Moyon, Quentin / Hausfater, Pierre / Chasset, Francois / Haroche, Julien / Cohen-Aubart, Fleur / Mathian, Alexis / Amoura, Zahir

    Annals of the rheumatic diseases

    2024  Volume 83, Issue 4, Page(s) 541–543

    MeSH term(s) Humans ; Antibodies, Monoclonal, Humanized ; Immunosuppressive Agents ; Lupus Erythematosus, Systemic ; Treatment Outcome
    Chemical Substances belimumab (73B0K5S26A) ; Antibodies, Monoclonal, Humanized ; Immunosuppressive Agents
    Language English
    Publishing date 2024-03-12
    Publishing country England
    Document type Letter
    ZDB-ID 7090-7
    ISSN 1468-2060 ; 0003-4967
    ISSN (online) 1468-2060
    ISSN 0003-4967
    DOI 10.1136/ard-2023-225023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A Score to Predict the Clinical Usefulness of Therapeutic Drug Monitoring: Application to Oral Molecular Targeted Therapies in Cancer.

    Géraud, Arthur / Combarel, David / Funck-Brentano, Christian / Beaulieu, Quentin / Zahr, Noël / Broutin, Sophie / Spano, Jean-Philippe / Massard, Christophe / Besse, Benjamin / Gougis, Paul

    Clinical pharmacology and therapeutics

    2024  

    Abstract: Therapeutic drug monitoring (TDM) involves measuring and interpreting drug concentrations in biological fluids to adjust drug dosages. In onco-hematology, TDM guidelines for oral molecular targeted therapies (oMTTs) are varied. This study evaluates a ... ...

    Abstract Therapeutic drug monitoring (TDM) involves measuring and interpreting drug concentrations in biological fluids to adjust drug dosages. In onco-hematology, TDM guidelines for oral molecular targeted therapies (oMTTs) are varied. This study evaluates a quantitative approach with a score to predict the clinical usefulness of TDM for oMTTs. We identified key parameters for an oMTT's suitability for TDM from standard TDM recommendations. We gathered oMTT pharmacological data, which covered exposure variability (considering pharmacokinetic (PK) impact of food and proton pump inhibitors), technical intricacy (PK linearity and active metabolites), efficacy (exposure-response relationship), and safety (maximum tolerated dose, and exposure-safety relationship). To assess the validity and the relevance of the score and define relevant thresholds, we evaluated molecules with prospective validation or strong recommendations for TDM, both in oncology and in other fields. By September 1, 2021, the US Food and Drug Administration (FDA) approved 67 oMTTs for onco-hematological indications. Scores ranged from 15 (acalabrutinib) to 80 (sunitinib) with an average of 48.3 and a standard deviation of 15.6. Top scorers included sunitinib, sorafenib, cabozantinib, nilotinib, and abemaciclib. Based on scores, drugs were categorized into low (< 40), intermediate (≥ 40 and < 60), and high (≥ 60) relevance for TDM. Notably, negative controls generally scored around or under 40, whereas positive controls had a high score across different indications. In this work, we propose a quantitative and reproducible score to compare the potential usefulness of TDM for oMTTs. Future guidelines should prioritize the TDM for molecules with the highest score.
    Language English
    Publishing date 2024-02-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 123793-7
    ISSN 1532-6535 ; 0009-9236
    ISSN (online) 1532-6535
    ISSN 0009-9236
    DOI 10.1002/cpt.3193
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  6. Article ; Online: Simultaneous quantification of four hormone therapy drugs by LC-MS/MS: Clinical applications in breast cancer patients.

    Mansour, Bochra / Ngo, Clarice / Schlemmer, Dimitri / Robidou, Pascal / Blondel, Juliette / Marin, Clémence / Noé, Gaëlle / Procureur, Adrien / Jamelot, Mathieu / Gligorov, Joseph / Salem, Joe-Elie / Zahr, Noël

    Journal of pharmaceutical and biomedical analysis

    2024  Volume 242, Page(s) 116032

    Abstract: Introduction: Aromatase inhibitors such as anastrozole, letrozole, exemestane and selective estrogen down-regulator (SERD) fulvestrant are used mostly to treat breast cancer estrogen receptor positive in post-menopausal women. These drugs are given ... ...

    Abstract Introduction: Aromatase inhibitors such as anastrozole, letrozole, exemestane and selective estrogen down-regulator (SERD) fulvestrant are used mostly to treat breast cancer estrogen receptor positive in post-menopausal women. These drugs are given either through the oral route or by intramuscular injection. They have shown great inter-individual variability with a risk of cardiometabolic disorders. Hence the importance of their therapeutic drug monitoring not only for exposure-efficacy but also exposure-toxicity. We describe here a LC-MS/MS method for the simultaneous quantification of anastrozole, letrozole, exemestane and fulvestrant in human plasma.
    Material and methods: Plasma samples were prepared by a single-step protein precipitation. The liquid chromatography system was paired with a triple quadrupole mass spectrometer. Quantification were achieved in Multiple Reactions Monitoring mode and the electrospray ionization was in positive mode.
    Results: The method demonstrated consistent analytical performance across various parameters, including linearity, specificity, sensitivity, matrix effect, upper and lower limits of quantification, extraction recovery, precision, accuracy, hemolysis effect, dilution integrity, and stability under different storage conditions, in accordance with established guidelines. The analysis time for each run was 4 min. Calibration curves exhibited linearity within the 1-100 ng/mL range, with correlation coefficients > 0.99 for the four analytes. Plasma concentrations from 42 patients were integrated into the selected calibration. Stability assessments indicated that the four drugs remained stable at - 20 °C for three months, 15 days under refrigeration, up to 7 days at room temperature, and after three freeze-thaw cycles.
    Conclusion: We have developed and validated this quantitative method for therapeutic drug monitoring of those four hormone therapy drugs:anastrozole, letrozole, fulvestrant and exemestane. This method can be also used for future clinical pharmacokinetics /pharmacodynamics studies.
    MeSH term(s) Humans ; Female ; Breast Neoplasms/drug therapy ; Anastrozole/therapeutic use ; Letrozole/therapeutic use ; Chromatography, Liquid/methods ; Fulvestrant/therapeutic use ; Liquid Chromatography-Mass Spectrometry ; Tandem Mass Spectrometry/methods ; Reproducibility of Results
    Chemical Substances Anastrozole (2Z07MYW1AZ) ; Letrozole (7LKK855W8I) ; Fulvestrant (22X328QOC4)
    Language English
    Publishing date 2024-02-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 604917-5
    ISSN 1873-264X ; 0731-7085
    ISSN (online) 1873-264X
    ISSN 0731-7085
    DOI 10.1016/j.jpba.2024.116032
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Fonction rénale et traitement du cancer : quels problèmes pour l’oncologue ?

    Delaye, Matthieu / Zahr, Noël / Isnard-Bagnis, Corinne / Gougis, Paul / Campedel, Luca

    La Revue du praticien

    2021  Volume 71, Issue 2, Page(s) 206–211

    Title translation Kidney function and cancer treatment: which problems for the oncologist?
    MeSH term(s) Humans ; Kidney ; Neoplasms/therapy ; Oncologists ; Physician-Patient Relations
    Language French
    Publishing date 2021-06-23
    Publishing country France
    Document type Journal Article
    ZDB-ID 205365-2
    ISSN 2101-017X ; 0035-2640
    ISSN (online) 2101-017X
    ISSN 0035-2640
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  8. Article ; Online: Identification of new risk factors for hydroxychloroquine and chloroquine retinopathy in systemic lupus erythematosus patients.

    Trefond, Ludovic / Lhote, Raphael / Mathian, Alexis / de Chambrun, Marc Pineton / Pha, Micheline / Hie, Miguel / Miyara, Makoto / Papo, Matthias / Moyon, Quentin / Taieb, Dov / Saade, Sonia / Salem, Thouraya Ben / Haroche, Julien / Chasset, François / Aubart, Fleur Cohen / Zahr, Noël / Amoura, Zahir

    Seminars in arthritis and rheumatism

    2024  Volume 66, Page(s) 152417

    Abstract: Background: Long-term hydroxychloroquine (HCQ) or chloroquine (CQ) intake causes retinal toxicity in 0.3-8 % of patients with rheumatic diseases. Numerous risk factors have been described, eg, daily dose by weight, treatment duration, chronic kidney ... ...

    Abstract Background: Long-term hydroxychloroquine (HCQ) or chloroquine (CQ) intake causes retinal toxicity in 0.3-8 % of patients with rheumatic diseases. Numerous risk factors have been described, eg, daily dose by weight, treatment duration, chronic kidney disease, concurrent tamoxifen therapy and pre-existing retinal or macular disease. However, those factors cannot explain the entire risk of developing antimalarial retinopathy.
    Objective: This study was undertaken to identify new risk factors associated with HCQ or CQ retinopathy (QRNP) in systemic lupus erythematosus (SLE) patients.
    Methods: This case-control (1:2) study compared SLE patients with QRNP (cases) to those without (controls). Controls were matched for sex and known QRNP risk factors: HCQ and/or CQ treatment duration (±1 year) and age (±5 year) at SLE diagnosis.
    Results: Forty-eight cases were compared to 96 SLE controls. Multivariable logistic-regression analysis retained the following as independent determinants significantly associated with QRNP: concomitant selective serotonin-reuptake inhibitor (SSRI) or serotonin- and norepinephrine-reuptake inhibitor (SNRI) intake (OR [95 % confidence interval] 6.6 [1.2 to 40.9]; p < 0.01); antiphospholipid syndrome (OR=8.9 [2.2 to 41.4] p < 0.01); blood hydroxychloroquine/desethylchloroquine concentration ([HCQ]/[DCQ]) ratio <7.2 (OR 8.4 [2.7 to 30.8]; p < 0.01) or skin phototype ≥4 (OR 5.5 [1.4 to 26.5]; p = 0.02), but not daily HCQ dose, blood [HCQ] or body mass index.
    Conclusion: The results of this case-control study identified blood [HCQ]/[DCQ] ratio, concurrent SSRI/SNRI therapy, skin phototype ≥4 and antiphospholipid syndrome as new risk factors for QRNP.
    Language English
    Publishing date 2024-02-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 120247-9
    ISSN 1532-866X ; 0049-0172
    ISSN (online) 1532-866X
    ISSN 0049-0172
    DOI 10.1016/j.semarthrit.2024.152417
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  9. Article ; Online: Corrigendum to "Pharmacokinetics/pharmacodynamics of ceftobiprole in patients on extracorporeal membrane oxygenation" [International Journal of Antimicrobial Agents Volume 61 (2023)106765].

    Coppens, Alexandre / Zahr, Noël / Chommeloux, Juliette / Bleibtreu, Alexandre / Hekimian, Guillaume / Pineton de Chambrun, Marc / LeFevre, Lucie / Schmidt, Matthieu / Robert, Jérôme / Junot, Helga / Combes, Alain / Luyt, Charles-Edouard

    International journal of antimicrobial agents

    2023  Volume 61, Issue 6, Page(s) 106814

    Language English
    Publishing date 2023-04-19
    Publishing country Netherlands
    Document type Published Erratum
    ZDB-ID 1093977-5
    ISSN 1872-7913 ; 0924-8579
    ISSN (online) 1872-7913
    ISSN 0924-8579
    DOI 10.1016/j.ijantimicag.2023.106814
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  10. Article ; Online: Determination of plasma concentration of Belimumab by LC-MS/MS: Method development, validation, and clinical application.

    Marin, Clémence / Noé, Gaëlle / Schlemmer, Dimitri / Beaulieu, Quentin / Robidou, Pascal / Mansour, Bochra / Hirtz, Christophe / Vialaret, Jérôme / Antignac, Marie / Moyon, Quentin / Benameur, Neila / Amoura, Zahir / Zahr, Noël

    Journal of pharmaceutical and biomedical analysis

    2023  Volume 236, Page(s) 115730

    Abstract: Introduction: Belimumab is a monoclonal antibody against B cell activating factor (BLyS). This monoclonal antibody (mAb) has been shown to be effective in reducing disease activity in patients with systemic lupus erythematosus (SLE). Belimumab is ... ...

    Abstract Introduction: Belimumab is a monoclonal antibody against B cell activating factor (BLyS). This monoclonal antibody (mAb) has been shown to be effective in reducing disease activity in patients with systemic lupus erythematosus (SLE). Belimumab is available in two forms as a lyophilized powder for intravenous (IV) use, or single-dose syringe for subcutaneous (SC) use. The aim of this study was to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantitation of belimumab in human serum.
    Material and methods: All analyses relied on nano-surface and molecular-orientation limited (nSMOL) proteolysis coupled with LC-MS/MS. Quantifications was performed in multiple reactions monitoring (MRM) mode, and electrospray ionization was conducted in positive mode.
    Results: Belimumab was quantified with signature peptide QAPGQGLEWMGGIPFGTAK and normalized using P14R. The total run time per assay was 10 min. Linearity was measured from 5 to 800 μg/mL (r² > 0.995). Accuracy and precision based on three quality control levels range from 11.2 - 9.51 % and 1.24 - 13.12 % respectively. The carryover was less than 7 %. In all, 87 patient samples were processed (65, IV; 22, SC). Mean concentration of belimumab was significantly higher for SC (93.0 ± 74.0 µg/mL) than for IV (67.4 ± 38.9 µg/mL) administration.
    Conclusion: We have developed the first method of belimumab quantification combining LC-MS/MS and nSMOL proteolysis. It can be used for future clinical pharmacokinetic studies of belimumab and for investigating the relationship between belimumab concentration, efficacy, and toxicity in SLE patients.
    Language English
    Publishing date 2023-09-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 604917-5
    ISSN 1873-264X ; 0731-7085
    ISSN (online) 1873-264X
    ISSN 0731-7085
    DOI 10.1016/j.jpba.2023.115730
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