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  1. AU="Azzopardi, Nicolas"
  2. AU="Surić-Mihić Marija"
  3. AU=Cismasiu Valeriu B
  4. AU="Töpfer, Änne"
  5. AU="Lemcke, Johannes"
  6. AU=Cousins Emily
  7. AU="Clarke Aileen"
  8. AU="Aparecido Corrêa, Nivaldo"
  9. AU="Meng-Ju Wang"
  10. AU=Verrills Paul
  11. AU="Chaudhari, Amol"
  12. AU="Planagumà, Jesús"
  13. AU="de Rezende, Grazielli Rocha"
  14. AU="Mohadeseh NEZAM"
  15. AU="Daniel Pecos-Martín"
  16. AU="Gentle, Popular"
  17. AU=Wang Jirui
  18. AU="Bielik, Martin"
  19. AU="Simon A.F. Darroch"
  20. AU="Suzuki, Kenichi G N"
  21. AU="Hu, Yizhong"
  22. AU=Sasaki Kotaro
  23. AU=Abd-Elsayed Alaa
  24. AU="Jung, Hee-Jun"
  25. AU="Struckmann, Stephan"
  26. AU=Coward Richard
  27. AU="Ghazizadeh, Shabnam"
  28. AU="Rebecca A Butcher"
  29. AU="Kimberlyn Roosa"
  30. AU=Chian Ri-Cheng
  31. AU="Alzalzalah, Sayed"
  32. AU=Kaufman Jonathan J
  33. AU="Kim, Jin K"
  34. AU="Zevakov, S A"
  35. AU="Sui Phang"
  36. AU="Kolomeichuk, Lilia V"
  37. AU="Sabuj Kanti Mistry"
  38. AU="Basurto-Lozada, Daniela"
  39. AU="Takashima, Shin-Ichiro"
  40. AU="Teresinha Leal"
  41. AU="Angélique B van 't Wout"
  42. AU="Roberts, Nicholas J"
  43. AU="Chauhan, Gaurav B"
  44. AU=Hanjaya-Putra Donny
  45. AU=Powell James
  46. AU="Russell, Todd"
  47. AU=Forth Scott
  48. AU="Kreutzer, Susanne" AU="Kreutzer, Susanne"
  49. AU="St John, Maie"
  50. AU=Gerhardy A
  51. AU="Qi, Huixin"
  52. AU="Dobosiewicz, May"
  53. AU="Srivastava, Rakesh"
  54. AU="Grevtsov K.I."

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  1. Artikel ; Online: Albumin influences leucocyte FcRn expression in the early days of kidney transplantation.

    Boulard, Pierre / Azzopardi, Nicolas / Levard, Romain / Cornec, Jean-Marie / Lamamy, Juliette / Prieur, Bérénice / Demattei, Marie-Véronique / Watier, Hervé / Gatault, Philippe / Gouilleux-Gruart, Valérie

    Clinical and experimental immunology

    2024  Band 216, Heft 3, Seite(n) 307–317

    Abstract: FcRn, a receptor originally known for its involvement in IgG and albumin transcytosis and recycling, is also important in the establishment of the innate and adaptive immune response. Dysregulation of the immune response has been associated with ... ...

    Abstract FcRn, a receptor originally known for its involvement in IgG and albumin transcytosis and recycling, is also important in the establishment of the innate and adaptive immune response. Dysregulation of the immune response has been associated with variations in FcRn expression, as observed in cancer. Recently, a link between autophagy and FcRn expression has been demonstrated. Knowing that autophagy is strongly involved in the development of reperfusion injury in kidney transplantation and that albuminemia is transiently decreased in the first 2 weeks after transplantation, we investigated variations in FcRn expression after kidney transplantation. We monitored FcRn levels by flow cytometry in leukocytes from 25 renal transplant patients and considered parameters such as albumin concentrations, estimated glomerular filtration rate, serum creatinine, serum IgG levels, and ischaemia/reperfusion time. Two groups of patients could be distinguished according to their increased or non-increased FcRn expression levels between days 2 and 6 (d2-d6) post-transplantation. Leukocyte FcRn expression at d2-d6 was correlated with albumin concentrations at d0-d2. These results suggest that albumin concentrations at d0-d2 influence FcRn expression at d2-d6, raising new questions about the mechanisms underlying these original observations.
    Mesh-Begriff(e) Humans ; Kidney Transplantation ; Receptors, Fc/metabolism ; Receptors, Fc/genetics ; Histocompatibility Antigens Class I/genetics ; Histocompatibility Antigens Class I/metabolism ; Histocompatibility Antigens Class I/immunology ; Male ; Female ; Middle Aged ; Leukocytes/immunology ; Leukocytes/metabolism ; Adult ; Aged ; Immunoglobulin G/immunology ; Glomerular Filtration Rate ; Serum Albumin
    Chemische Substanzen Fc receptor, neonatal
    Sprache Englisch
    Erscheinungsdatum 2024-02-14
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 218531-3
    ISSN 1365-2249 ; 0009-9104 ; 0964-2536
    ISSN (online) 1365-2249
    ISSN 0009-9104 ; 0964-2536
    DOI 10.1093/cei/uxae011
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Relationship Between Cetuximab Target-Mediated Pharmacokinetics and Progression-Free Survival in Metastatic Colorectal Cancer Patients.

    Lobet, Sarah / Paintaud, Gilles / Azzopardi, Nicolas / Passot, Christophe / Caulet, Morgane / Chautard, Romain / Desvignes, Céline / Capitain, Olivier / Tougeron, David / Lecomte, Thierry / Ternant, David

    Clinical pharmacokinetics

    2023  Band 62, Heft 9, Seite(n) 1263–1274

    Abstract: Background and objective: Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal immunoglobulin (Ig)G1 antibody, has been approved for the treatment of metastatic colorectal cancer (mCRC). The influence of target-antigen on cetuximab ... ...

    Abstract Background and objective: Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal immunoglobulin (Ig)G1 antibody, has been approved for the treatment of metastatic colorectal cancer (mCRC). The influence of target-antigen on cetuximab pharmacokinetics has never been investigated using target-mediated drug disposition (TMDD) modelling. This study aimed to investigate the relationship between cetuximab concentrations, target kinetics and progression-free survival (PFS).
    Methods: In this ancillary study (NCT00559741), 91 patients with mCRC treated with cetuximab were assessed. Influence of target levels on cetuximab pharmacokinetics was described using TMDD modelling. The relationship between cetuximab concentrations, target kinetics and time-to-progression (TTP) was described using a joint pharmacokinetic-TTP model, where unbound target levels were assumed to influence hazard of progression by an E
    Results: Cetuximab concentration-time data were satisfactorily described using the TMDD model with quasi-steady-state approximation and time-varying endogenous clearance. Estimated target parameters were baseline target levels (R
    Conclusion: This is the first study describing the complex relationship between cetuximab target-mediated pharmacokinetics and PFS in mCRC patients using a joint PK-time-to-progression model. Further studies are needed to provide a more in-depth description of this relationship.
    Mesh-Begriff(e) Humans ; Cetuximab/therapeutic use ; Cetuximab/pharmacokinetics ; Progression-Free Survival ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antibodies, Monoclonal, Humanized/pharmacokinetics ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal/pharmacokinetics ; Antineoplastic Agents/therapeutic use ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/pathology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use
    Chemische Substanzen Cetuximab (PQX0D8J21J) ; Antibodies, Monoclonal, Humanized ; Antibodies, Monoclonal ; Antineoplastic Agents
    Sprache Englisch
    Erscheinungsdatum 2023-07-13
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 197627-8
    ISSN 1179-1926 ; 0312-5963
    ISSN (online) 1179-1926
    ISSN 0312-5963
    DOI 10.1007/s40262-023-01270-2
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  3. Artikel ; Online: Confounding mitigation for the exposure-response relationship of bevacizumab in colorectal cancer patients.

    Lobet, Sarah / Caulet, Morgane / Paintaud, Gilles / Azzopardi, Nicolas / Desvignes, Céline / Chautard, Romain / Borg, Christophe / Capitain, Olivier / Ferru, Aurélie / Bouché, Olivier / Lecomte, Thierry / Ternant, David

    British journal of clinical pharmacology

    2023  Band 90, Heft 4, Seite(n) 976–986

    Abstract: Aims: The exposure-response relationship of bevacizumab may be confounded by various factors, including baseline characteristics, time-dependent target engagement and recursive relationships between exposure and response, requiring effective mitigation. ...

    Abstract Aims: The exposure-response relationship of bevacizumab may be confounded by various factors, including baseline characteristics, time-dependent target engagement and recursive relationships between exposure and response, requiring effective mitigation. This study aimed to investigate the exposure-response relationships of bevacizumab in metastatic colorectal cancer (mCRC) patients while mitigating potential biases.
    Methods: Bevacizumab pharmacokinetics was described using target-mediated drug disposition modelling. Relationships between target kinetics, progression-free (PFS) and overall (OS) survivals were assessed using joint pharmacokinetic and parametric hazard function models. Both prognostic-driven and response-driven potential biases were mitigated. These models evaluated the impact of increased antigen target levels, clearance and intensified dosing regimen on survival.
    Results: Estimated target-mediated pharmacokinetic parameters in 130 assessed patients were baseline target levels (R
    Conclusion: This study is the first to demonstrate the relationship between bevacizumab concentrations, target involvement and clinical efficacy by effectively mitigating potential sources of bias. Most of the target amount may be tumoural in mCRC. Future studies should provide a more in-depth description of this relationship.
    Mesh-Begriff(e) Humans ; Bevacizumab ; Vascular Endothelial Growth Factor A ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/pathology ; Disease-Free Survival ; Treatment Outcome ; Rectal Neoplasms ; Antineoplastic Combined Chemotherapy Protocols ; Fluorouracil
    Chemische Substanzen Bevacizumab (2S9ZZM9Q9V) ; Vascular Endothelial Growth Factor A ; Fluorouracil (U3P01618RT)
    Sprache Englisch
    Erscheinungsdatum 2023-12-29
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 188974-6
    ISSN 1365-2125 ; 0306-5251 ; 0264-3774
    ISSN (online) 1365-2125
    ISSN 0306-5251 ; 0264-3774
    DOI 10.1111/bcp.15983
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  4. Artikel ; Online: Predictors of response to TNF inhibitors in rheumatoid arthritis: an individual patient data pooled analysis of randomised controlled trials.

    Law-Wan, Johan / Sparfel, Marc-Antoine / Derolez, Sophie / Azzopardi, Nicolas / Goupille, Philippe / Detert, Jacqueline / Mulleman, Denis / Bejan-Angoulvant, Theodora

    RMD open

    2021  Band 7, Heft 3

    Abstract: Objective: To identify patient characteristics associated with responsiveness to tumour necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA).: Materials and methods: Individual patient data from 29 randomised controlled trials (RCTs) ... ...

    Abstract Objective: To identify patient characteristics associated with responsiveness to tumour necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA).
    Materials and methods: Individual patient data from 29 randomised controlled trials (RCTs) evaluating the efficacy of a TNFi versus placebo or conventional therapy were obtained. Response to treatment was assessed in subgroups according to the following baseline characteristics: smoking status, physical activity, sex, age, body mass index, autoantibody profile, disease duration, high initial disease activity defined by Disease Activity Score on 28 joints (DAS28)(C reactive protein (CRP)) >5.1. The primary outcome was the between-treatment group difference in DAS28(CRP) change from baseline to 6 months. The secondary endpoints were the between-treatment group difference in final DAS28(CRP) measured until 6 months and EULAR response criteria until 6 months. Data from each RCT were then pooled by the Mantel-Haenszel method using a random effects model. A linear metaregression was also carried out on two data-sharing platforms separately to support the results.
    Results: Individual data of 11 617 patients from 29 RCTs were analysed. Until 6 months, a significantly higher EULAR non-response rate was observed in obese patients (OR 0.52 vs 0.36 for non-obese, p=0.01). A multivariable regression model performed on 7457 patients indicated that patients treated by TNFi had a final DAS28(CRP) decreased by 0.02 for each year of disease duration (p<0.001), and a 0.21 decreased for patients with a baseline DAS28(CRP) >5.1 (p<0.001).
    Conclusions: In RA, patients who are more responsive to TNFi are those who are non-obese, have a long disease duration and have a high initial disease activity.
    Mesh-Begriff(e) Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/drug therapy ; C-Reactive Protein ; Humans ; Randomized Controlled Trials as Topic ; Severity of Illness Index ; Tumor Necrosis Factor Inhibitors
    Chemische Substanzen Antirheumatic Agents ; Tumor Necrosis Factor Inhibitors ; C-Reactive Protein (9007-41-4)
    Sprache Englisch
    Erscheinungsdatum 2021-12-09
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2812592-7
    ISSN 2056-5933 ; 2056-5933
    ISSN (online) 2056-5933
    ISSN 2056-5933
    DOI 10.1136/rmdopen-2021-001882
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Relationship Between Antithymocyte Globulin Concentrations and Lymphocyte Sub-Populations in Kidney Transplant Patients.

    Azzopardi, Nicolas / Longuet, Hélène / Ternant, David / Thibault, Gilles / Gouilleux-Gruart, Valérie / Lebranchu, Yvon / Büchler, Matthias / Gatault, Philippe / Paintaud, Gilles

    Clinical pharmacokinetics

    2021  Band 61, Heft 1, Seite(n) 111–122

    Abstract: Background: Rabbit antithymocyte globulins (rATGs) are polyclonal antibodies used to prevent acute cellular rejection in kidney transplantation. Their dosing remains largely empirical and the question of an individualized dose is still unresolved.: ... ...

    Abstract Background: Rabbit antithymocyte globulins (rATGs) are polyclonal antibodies used to prevent acute cellular rejection in kidney transplantation. Their dosing remains largely empirical and the question of an individualized dose is still unresolved.
    Methods: Data from a prospective study in 17 kidney transplant patients were used to develop a model describing the dose-concentration-response relationship of rATG with T-lymphocyte subpopulation counts over time. The model was validated using an independent cohort of kidney transplant patients treated by rATG in the same center.
    Results: Pharmacokinetics of rATG was described using a two-compartment model integrating a third compartment and a target-mediated elimination for active rATG. The kinetics of CD3
    Conclusions: Our results can be used to design prospective clinical trials testing dose individualization based on patients' characteristics.
    Clinical trial registration: Eudract No. 2009-012673-35.
    Mesh-Begriff(e) Aged ; Antilymphocyte Serum ; Graft Rejection ; Humans ; Immunosuppressive Agents ; Kidney Transplantation ; Lymphocyte Subsets ; Prospective Studies ; Receptors, IgG
    Chemische Substanzen Antilymphocyte Serum ; FCGR3A protein, human ; Immunosuppressive Agents ; Receptors, IgG
    Sprache Englisch
    Erscheinungsdatum 2021-07-22
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 197627-8
    ISSN 1179-1926 ; 0312-5963
    ISSN (online) 1179-1926
    ISSN 0312-5963
    DOI 10.1007/s40262-021-01053-7
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  6. Artikel ; Online: CD4+ count-dependent concentration-effect relationship of rituximab in rheumatoid arthritis.

    Bensalem, Amina / Mulleman, Denis / Thibault, Gilles / Azzopardi, Nicolas / Goupille, Philippe / Paintaud, Gilles / Ternant, David

    British journal of clinical pharmacology

    2019  Band 85, Heft 12, Seite(n) 2747–2758

    Abstract: Aims: Rituximab is approved in rheumatoid arthritis (RA). A substantial decrease in CD4+ count was observed in responders after a single cycle of treatment. This study aimed to describe and quantifying the influence of CD4+ count depletion on the ... ...

    Abstract Aims: Rituximab is approved in rheumatoid arthritis (RA). A substantial decrease in CD4+ count was observed in responders after a single cycle of treatment. This study aimed to describe and quantifying the influence of CD4+ count depletion on the concentration-response relationship of rituximab in RA patients.
    Methods: In this retrospective monocentric observational study, 52 patients were assessed. Repeated measurements of rituximab concentrations (pharmacokinetics), CD4+ counts (biomarker) and disease activity score in 28 joints (DAS28, clinical response) were made. Rituximab pharmacokinetics was described using a 2-compartment model, and CD4+ cell counts and DAS28 measurements were described using indirect turnover and direct Emax pharmacokinetic-pharmacodynamic models, respectively. Delay between rituximab concentrations and responses was accounted for by including biophase compartments.
    Results: Elimination half-life of rituximab was 18 days. The pharmacokinetic-pharmacodynamic model showed that DAS28 response to rituximab was partly associated with CD4+ cell depletion. At 6 months, a deeper DAS28 decrease was observed in patients when CD4+ cell count is decreased: median [interquartile range] of DAS28 was 3.7 [2.9-4.4] and 4.5 [3.7-5.3] in patients with and without CD4+ decrease, respectively.
    Conclusions: This is the first study to quantify the relationship between rituximab concentrations, CD4+ count and DAS28 in RA patients. This model showed that approximately 75% of patients had CD4+ count decrease, and that the clinical improvement is 2-fold higher in patients with CD4+ cells decrease than in others.
    Mesh-Begriff(e) Adult ; Aged ; Aged, 80 and over ; Antirheumatic Agents/administration & dosage ; Antirheumatic Agents/adverse effects ; Antirheumatic Agents/blood ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/blood ; Arthritis, Rheumatoid/drug therapy ; Biomarkers/analysis ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes/drug effects ; Dose-Response Relationship, Drug ; Female ; Half-Life ; Humans ; Male ; Markov Chains ; Middle Aged ; Models, Biological ; Retrospective Studies ; Rituximab/administration & dosage ; Rituximab/adverse effects ; Rituximab/blood ; Rituximab/therapeutic use ; Treatment Outcome
    Chemische Substanzen Antirheumatic Agents ; Biomarkers ; Rituximab (4F4X42SYQ6)
    Sprache Englisch
    Erscheinungsdatum 2019-11-22
    Erscheinungsland England
    Dokumenttyp Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 188974-6
    ISSN 1365-2125 ; 0306-5251 ; 0264-3774
    ISSN (online) 1365-2125
    ISSN 0306-5251 ; 0264-3774
    DOI 10.1111/bcp.14102
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  7. Artikel ; Online: Influence of Antigen Mass on the Pharmacokinetics of Therapeutic Antibodies in Humans.

    Ternant, David / Azzopardi, Nicolas / Raoul, William / Bejan-Angoulvant, Theodora / Paintaud, Gilles

    Clinical pharmacokinetics

    2018  Band 58, Heft 2, Seite(n) 169–187

    Abstract: Therapeutic antibodies are increasingly used to treat various diseases, including neoplasms and chronic inflammatory diseases. Antibodies exhibit complex pharmacokinetic properties, notably owing to the influence of antigen mass, i.e. the amount of ... ...

    Abstract Therapeutic antibodies are increasingly used to treat various diseases, including neoplasms and chronic inflammatory diseases. Antibodies exhibit complex pharmacokinetic properties, notably owing to the influence of antigen mass, i.e. the amount of antigenic targets to which the monoclonal antibody binds specifically. This review focuses on the influence of antigen mass on the pharmacokinetics of therapeutic antibodies quantified by pharmacokinetic modelling in humans. Out of 159 pharmacokinetic studies, 85 reported an influence of antigen mass. This influence led to non-linear elimination decay in 50 publications, which was described using target-mediated drug disposition or derived models, as quasi-steady-state, irreversible binding and Michaelis-Menten models. In 35 publications, the pharmacokinetics was apparently linear and the influence of antigen mass was described as a covariate of pharmacokinetic parameters. If some reported covariates, such as the circulating antigen level or tumour size, are likely to be correlated to antigen mass, others, such as disease activity or disease type, may contain little information on the amount of antigenic targets. In some cases, antigen targets exist in different forms, notably in the circulation and expressed at the cell surface. The influence of antigen mass should be soundly described during the early clinical phases of drug development. To maximise therapeutic efficacy, sufficient antibody doses should be administered to ensure the saturation of antigen targets by therapeutic antibodies in all patients. If necessary, antigen mass should be taken into account in routine clinical practice.
    Mesh-Begriff(e) Animals ; Antibodies, Monoclonal/pharmacokinetics ; Antibodies, Monoclonal/therapeutic use ; Antigens ; Dose-Response Relationship, Immunologic ; Humans ; Models, Biological
    Chemische Substanzen Antibodies, Monoclonal ; Antigens
    Sprache Englisch
    Erscheinungsdatum 2018-05-24
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 197627-8
    ISSN 1179-1926 ; 0312-5963
    ISSN (online) 1179-1926
    ISSN 0312-5963
    DOI 10.1007/s40262-018-0680-3
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  8. Artikel ; Online: Cetuximab pharmacokinetics influences overall survival in head and neck cancer patients.

    Pointreau, Yoann / Azzopardi, Nicolas / Ternant, David / Calais, Gilles / Paintaud, Gilles

    Therapeutic drug monitoring

    2016  

    Abstract: Background: A retrospective study was conducted to analyze interindividual variability of cetuximab pharmacokinetics and its influence on survival (Progression Free Survival - PFS and overall survival - OS) in a cohort of head and neck squamous cell ... ...

    Abstract Background: A retrospective study was conducted to analyze interindividual variability of cetuximab pharmacokinetics and its influence on survival (Progression Free Survival - PFS and overall survival - OS) in a cohort of head and neck squamous cell carcinoma (HNSCC).
    Methods: Thirty-four patients received cetuximab as an infusion loading dose of 400 mg/m followed by weekly infusions of 250 mg/m. Twenty-one patients had locally advanced HNSCC (LAHNSCC) and thirteen had metastatic/recurrent HNSCC (MHNSCC). Cetuximab concentrations were measured by ELISA and its pharmacokinetics was analyzed by a population approach. Survivals were analyzed with the log-rank test.
    Results: Cetuximab pharmacokinetics was best described using a two-compartment model with both first-order and saturable (zero-order) eliminations. Estimated pharmacokinetic parameters (%CV) were: central volume of distribution V1 = 3.18 L (6%), peripheral volume of distribution V2 = 5.4 L (42%), elimination clearance CL = 0.57 L/day (31%), distribution clearance Q = 0.64 L/day, and zero-order elimination rate k0 = 6.72 mg/day (29%). Both V1 and V2 increased with body surface area. Adjunction of chemotherapy reduced CL and increased k0. Overall survival was inversely related with cetuximab global clearance (p = 0.007) and was higher in patients with severe radiation dermatitis (p = 0.005).
    Conclusion: Cetuximab pharmacokinetics in HNSCC patients can be described using a two-compartment model combining linear and nonlinear mechanisms of elimination. Overall survival is associated with both cetuximab global clearance and severe radiation dermatitis.
    Sprache Englisch
    Erscheinungsdatum 2016-07-04
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 424443-6
    ISSN 1536-3694 ; 0163-4356
    ISSN (online) 1536-3694
    ISSN 0163-4356
    DOI 10.1097/FTD.0000000000000321
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  9. Artikel ; Online: Cetuximab Pharmacokinetics Influences Overall Survival in Patients With Head and Neck Cancer.

    Pointreau, Yoann / Azzopardi, Nicolas / Ternant, David / Calais, Gilles / Paintaud, Gilles

    Therapeutic drug monitoring

    2016  Band 38, Heft 5, Seite(n) 567–572

    Abstract: Background: A retrospective study was conducted to analyze interindividual variability of cetuximab pharmacokinetics and its influence on survival (progression-free survival and overall survival [OS]) in a cohort of head and neck squamous cell carcinoma ...

    Abstract Background: A retrospective study was conducted to analyze interindividual variability of cetuximab pharmacokinetics and its influence on survival (progression-free survival and overall survival [OS]) in a cohort of head and neck squamous cell carcinoma (HNSCC).
    Methods: Thirty-four patients received cetuximab as an infusion loading dose of 400 mg/m followed by weekly infusions of 250 mg/m. Twenty-one patients had locally advanced HNSCC, and 13 had metastatic/recurrent HNSCC. Cetuximab concentrations were measured by the enzyme-linked immunosorbent assay, and its pharmacokinetics was analyzed by a population approach. Survivals were analyzed with the log-rank test.
    Results: Cetuximab pharmacokinetics was best described using a 2-compartment model with both first-order and saturable (zero-order) eliminations. Estimated pharmacokinetic parameters (%CV) were central volume of distribution V1 = 3.18 L (6%), peripheral volume of distribution V2 = 5.4 L (42%), elimination clearance CL = 0.57 L/d (31%), distribution clearance Q = 0.64 L/d, and zero-order elimination rate k0 = 6.72 mg/d (29%). Both V1 and V2 increased with the body surface area. Adjunction of chemotherapy reduced CL and increased k0. OS was inversely related with cetuximab global clearance (P = 0.007) and was higher in patients with severe radiation dermatitis (P = 0.005).
    Conclusions: Cetuximab pharmacokinetics in patients with HNSCC can be described using a 2-compartment model combining linear and nonlinear mechanisms of elimination. OS is associated with both cetuximab global clearance and severe radiation dermatitis.
    Mesh-Begriff(e) Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized/blood ; Antibodies, Monoclonal, Humanized/pharmacokinetics ; Antibodies, Monoclonal, Humanized/therapeutic use ; Carcinoma, Squamous Cell/blood ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/metabolism ; Cetuximab/blood ; Cetuximab/pharmacokinetics ; Cetuximab/therapeutic use ; Disease-Free Survival ; Female ; Head and Neck Neoplasms/blood ; Head and Neck Neoplasms/drug therapy ; Head and Neck Neoplasms/metabolism ; Humans ; Male ; Middle Aged ; Models, Biological ; Retrospective Studies ; Squamous Cell Carcinoma of Head and Neck
    Chemische Substanzen Antibodies, Monoclonal, Humanized ; Cetuximab (PQX0D8J21J)
    Sprache Englisch
    Erscheinungsdatum 2016-09-08
    Erscheinungsland United States
    Dokumenttyp Clinical Trial ; Journal Article
    ZDB-ID 424443-6
    ISSN 1536-3694 ; 0163-4356
    ISSN (online) 1536-3694
    ISSN 0163-4356
    DOI 10.1097/FTD.0000000000000321
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: Antigen Mass May Influence Trastuzumab Concentrations in Cerebrospinal Fluid After Intrathecal Administration.

    Le Tilly, Olivier / Azzopardi, Nicolas / Bonneau, Claire / Desvignes, Céline / Oberkampf, Florence / Ezzalfani, Monia / Ternant, David / Turbiez, Isabelle / Gutierrez, Maya / Paintaud, Gilles

    Clinical pharmacology and therapeutics

    2021  Band 110, Heft 1, Seite(n) 210–219

    Abstract: Intravenous administration of monoclonal antibodies leads to low concentrations in the central nervous system, which is a serious concern in neuro-oncology, especially in leptomeningeal carcinomatosis of HER2-overexpressing breast cancer. Case reports of ...

    Abstract Intravenous administration of monoclonal antibodies leads to low concentrations in the central nervous system, which is a serious concern in neuro-oncology, especially in leptomeningeal carcinomatosis of HER2-overexpressing breast cancer. Case reports of i.t. administrations of trastuzumab have shown promising results in these patients but dosing regimens are empirical in absence of pharmacokinetic (PK) study. With a population PK approach, we described the fate of trastuzumab after i.t. administration in 21 women included in a phase I-II clinical trial. Trastuzumab was administered by i.t. route every week for 8 weeks and both cerebrospinal fluid (CSF) and serum were sampled to measure trough concentrations. Some patients showed noticeable CSF concentration fluctuations predicted using a target-mediated drug disposition. This target was latent and produced with a delayed feedback. Apparent volumes of distribution were close to physiological volumes (V
    Sprache Englisch
    Erscheinungsdatum 2021-03-31
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 123793-7
    ISSN 1532-6535 ; 0009-9236
    ISSN (online) 1532-6535
    ISSN 0009-9236
    DOI 10.1002/cpt.2188
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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