Pierre Marquet

French Institute of Health and Medical Research, Lutetia Parisorum, Île-de-France, France

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Publications (256)814.15 Total impact

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    ABSTRACT: Hepatitis C virus-related B-cell proliferation is a model of virus-driven autoimmune/neoplastic disorder leading to mixed cryoglobulinemia and/or B-cell non Hodgkin lymphoma. These lymphomas are often marginal zone lymphomas or diffuse large B-cell lymphomas. Peginterferon/Ribavirin therapy has proved its crucial role in the cure of these non-Hodgkin lymphomas, but data are lacking concerning new direct anti-viral agents. We report five cases of Hepatitis C virus-associated B-cell non Hodgkin lymphoma treated with direct anti-viral agents: two marginal zone lymphomas received direct anti-viral agents alone (one with a leukemic phase only, one with splenic and deep lymph nodes localizations); one renal marginal zone lymphoma with renal insufficiency received direct anti-viral agents and 4 rituximab infusions simultaneously; two diffuse large B-cell lymphomas were treated with direct ant-viral agents following chemotherapy. Sustained virological response was obtained in all patients, and complete remission of NHL was noted six months after cessation of any treatment except for one patient with a persistent small leukemic phase. Direct anti-viral agents might be proposed as a first-line treatment in marginal zone lymphomas in the case of no life-threatening complications with the precaution of a long-term follow-up. In the setting of diffuse large B-cell lymphomas, well-tolerated direct anti-viral agents could potentially be introduced very early not only to prevent relapse of these lymphomas but also to limit the liver toxicity of chemotherapy and rituximab by preventing outbreaks of viral load. New observations and trials should support these assumptions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 06/2015; DOI:10.1111/liv.12897
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    ABSTRACT: Ganciclovir (GCV) is prescribed for cytomegalovirus infection which is a major issue in immunodepressed patients. It is however characterized by hematological toxicity. A better understanding of GCV concentration-effects relationships implies the measurement of intracellular forms. The objective of this study was to develop a method to measure GCV and its derivatives in cells. A four-stage procedure was developed with the following strategy: (1) to separate into different fractions the different intracellular forms of GCV (GCV itself and its phosphorylated forms) by solid-phase extraction (SPE) from blood cells, (2) to dephosphorylate the different phosphorylated forms into GCV, (3) to perform a second SPE to desalt samples and concentrate GCV, and (4) to measure GCV concentrations in the different extracts using a triple-quadrupole, linear ion trap mass spectrometer. Finally, the procedure was tested in 17 patients receiving GCV. From lysed cells, the different forms of GCV were fractionated, the phosphorylated forms were eluted with different KCl solutions, and the obtained fractions were treated with acid phosphatase to transform the phosphorylated metabolites back into GCV. The method was validated from 5 to 500 μg L(-1) with a limit of detection of 1 μg L(-1). The whole procedure was validated according to the US Food and Drug Administration guidelines and successfully applied in 17 patients receiving GCV. The method liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) allowing the measurement of GCV and its phosphorylated forms in blood cells was developed and can be used in developing clinical studies to explore the role of these biomarkers in the event of toxicity.
    Analytical and Bioanalytical Chemistry 02/2015; 407(12). DOI:10.1007/s00216-015-8554-0
  • Gynécologie Obstétrique & Fertilité 01/2015; 43(2). DOI:10.1016/j.gyobfe.2014.12.005
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    ABSTRACT: To study the demand there is for uterus transplantation (UTx). Recent media coverage of developments in UTx prompted associations of patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome and of women suffering from UI to contact us. We sent them anonymous questionnaires devised to sound out their attitude towards UTx and towards adoption and gestational surrogacy (GS). A clinical psychologist also carried out a qualitative discourse analysis. Sixty patients answered the questionnaire. Thirty-eight patients were married or living with a male partner. Seven patients had had a hysterectomy. Fifty-one patients had uterine agenesis. Of the 60 patients, 19 and 21, respectively, had ruled out the option of adoption or GS, and 11 would not envisage either possibility. Thirty-five patients were willing to take part in a clinical study into UTx despite the uncertainty of the outcome and the potential risks involved. Of these 35 volunteers, 23 were in a heterosexual relationship and aged ≤35 years. For women with UI the condition is all the more distressing because there is no medical solution for it. UTx could hold out hope for some of these patients despite the complexity of the procedure and the attendant risks. Because of the feelings of vulnerability engendered by UI, any UTx programme should provide full information to patients and ensure they are carefully screened and selected. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
    Gynécologie Obstétrique & Fertilité 01/2015;
  • Gynécologie Obstétrique & Fertilité 11/2014; 42(11):741-3. DOI:10.1016/j.gyobfe.2014.09.010
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    ABSTRACT: BACKGROUND: Although therapeutic drug monitoring has improved the clinical use of immunosuppressive drugs, there is still interpatient variability in efficacy and toxicity that pharmacodynamic monitoring may help to reduce. To select the best biomarkers of tacrolimus pharmacodynamics, we explored the strength and variability of signal transduction and the influence of polymorphisms along the calcineurin pathway. METHODS: Peripheral blood mononuclear cells from 35 healthy volunteers were incubated with tacrolimus (0.1-50 ng/mL) and stimulated ex vivo. Inhibition of NFAT1 (nuclear factor of activated T cells 1) translocation to the nucleus and intracellular expression of interleukin-2 in CD4(+) and CD8(+) T cells and the surface activation marker CD25 in CD3(+) cells were measured by flow cytometry. We sequenced the promoter regions of immunophilins and calcineurin subunits and characterized selected single nucleotide polymorphisms in the genes of the calcineurin pathway with allelic discrimination assays. RESULTS: All responses closely fitted an I/Imax sigmoid model. Large interindividual variability (n = 30) in I-0 and IC50 was found for all biomarkers. Moreover, strong and statistically significant associations were found between tacrolimus pharmacodynamic parameters and polymorphisms in the genes coding cyclophilin A, the calcineurin catalytic subunit alpha isoenzyme, and CD25. CONCLUSIONS: This study demonstrates the consistency and large interindividual variability of signal transduction along the calcineurin pathway, as well as the strong influence of pharmacogenetic polymorphisms in the calcineurin cascade on both the physiological activity of this route and tacrolimus pharmacodynamics. (C) 2014 American Association for Clinical Chemistry
    Clinical Chemistry 08/2014; 60(10). DOI:10.1373/clinchem.2014.223511
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    ABSTRACT: A time to event model was developed to study predictive factors of immunosuppressive efficacy in renal transplant patients and to investigate longitudinal calcineurin inhibitors (CNIs) and mycophenolic acid (MPA) co-exposures, and patient characteristics as potential covariates. The efficacy endpoint included acute rejection, graft loss and death.Data from 222 patients were analyzed: 23 events were observed in 126 patients receiving cyclosporine against 15 in 96 patients receiving tacrolimus (p=0.61) in the two first years post-transplantation. Each 1mg.h/L increase of MPA AUC was associated with a 4% decreased risk of event (hazard ratio (HR) 95% confidence interval (CI): 0.93-0.99). The onset of cytomegalovirus infection/disease significantly increased this risk (HR=10.9; 95% CI: 6.5-21.7). Within the observed ranges, CNIs exposures were not significantly associated with efficacy (i.e. acute rejection, graft loss and death). This work advocates for the avoidance of unnecessary high CNIs dosing and puts forward new arguments for MPA concentration monitoring.Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 26 June 2014; doi:10.1038/clpt.2014.140.
    Clinical Pharmacology &#38 Therapeutics 06/2014; 96(4). DOI:10.1038/clpt.2014.140
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    ABSTRACT: In lung transplantation, diverse clinical events may impact patient outcome. In clinical trials comparing intervention strategies, single primary endpoints require large populations, or long study durations, whereas composite endpoints (CEPs) do not take into account the respective impact of their components on patient survival. The objective of this study was to propose consensus recommendations on endpoints for clinical trials on immunosuppressants in lung transplantation. The consensus process was managed through the Internet using the Delphi method. Forty experts were invited by the pilot group with the help of the International Society for Heart and Lung Transplantation and The Transplantation Society. In the first round, a questionnaire was made available to the experts to complete, and the responses were analyzed. In each next round, a new questionnaire was developed from the previous responses and sent to the panel members. Consensus between 17 experts was achieved after five rounds. Two score-type CEPs were defined for immunosuppressive drug efficacy (7 items) and for toxicity (15 items). Death related to graft loss or immunosuppressive drug toxicity was attributed a maximum weight of 100. The weights of the items included in the efficacy and toxicity CEPs ranged between 10 and 80 and between 25 and 70, respectively. The CEP scores are calculated by adding the weights of all the items composing them, without exceeding 90 as long as the patient is alive. This consensus conference proposed two score-type CEPs including relevant endpoints. After validation, they should allow clinical trials with higher statistical power, improving the evaluation of the interventions tested.
    Transplantation 06/2014; 98(12). DOI:10.1097/TP.0000000000000235
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    ABSTRACT: Purpose The aims of the present study were (1) to investigate the impact of great age on pharmacokinetics of capecitabine and its metabolites and (2) to evaluate the exposure–effect relationship of capecitabine in elderly patients. Methods Data collected from 20 elderly patients (75–92 years old) with breast or colorectal cancer who received oral capecitabine were analyzed. In order to study the old age effect on pharmacokinetics, data collected from two phase I studies involving 40 younger adults (<75 years old) with metastatic cancer who received oral capecitabine were added in the database. The population pharmacokinetic analysis was based on a four-compartment model describing the sequence of capecitabine and three of its metabolites. Results The absorption rate constant was found lower in the oldest patient group (≥75 years) compared with the youngest group, and the constant rate elimination of the 5-fluorouracil metabolite was found decreased over time (i.e., after 2 consecutive weeks of capecitabine administration). This time effect was not found different between the two age groups. In elderly patients, the exposure-safety analysis showed, from the second cycle of chemotherapy, significantly higher median exposures of capecitabine and its metabolites (5′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorouridine and 5-fluorouracil) in patients who experienced hand-foot syndrome compared with patients who did not. Conclusion This study puts forward new arguments for the treatment of elderly cancer patients who could benefit from capecitabine chemotherapy with acceptable toxicity.
    Cancer Chemotherapy and Pharmacology 06/2014; 73(6). DOI:10.1007/s00280-014-2466-0
  • Journal of Cystic Fibrosis 06/2014; 13:S107. DOI:10.1016/S1569-1993(14)60371-4
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    ABSTRACT: Objective: To describe the feasibility of human uterus retrieval after donation after brain death. Design: Single-center, prospective study. Setting: University hospital. Patient(s): Female brain dead donors. Intervention(s): The families of female brain dead donors were informed about consent to uterus donation. A specific organ retrieval procedure was performed. At the end of the procedure the uterus was removed together with the hypogastric vessels, parametria, and vaginal fornix. The tolerance of the uterus to cold ischemia was evaluated with histology and TUNEL reaction up to 24 hours. Main Outcome Measure(s): Rate of uterus donation refusal. Result(s): Between August 1, 2012 and July 31, 2013, seven uteri were retrieved from 14 female multiorgan donors. No refusal to uterus donation occurred. Our surgical protocol did not interfere with vital organ retrieval and was readily accepted by the other transplantation teams. The hypogastric vessels could be preserved in all cases but for one vein loss in the first retrieval. Histology studies did not find major morphologic changes after 24 hours of cold ischemia. Apoptosis was rare. Conclusion(s): Uterus retrieval could be part of a reproducible multiorgan procurement procedure. Uterus donation seems readily accepted. This preliminary study is a necessary step before any transplantation project. (C) 2014 by American Society for Reproductive Medicine.
    Fertility and Sterility 05/2014; 102(2). DOI:10.1016/j.fertnstert.2014.04.016
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    ABSTRACT: AimsThe use of mycophenolate mofetil (MMF) in children with Systemic Lupus Erythematosus (SLE) is increasing. However, the clinical benefit of its monitoring has been scarcely studied, and little is known about its pharmacokinetics in this context. The objectives of the present study were: (i) to describe mycophenolic acid (MPA; the active moiety of MMF) pharmacokinetics; (ii) to develop a Bayesian estimator (BE) allowing the determination AUC (Area under the curve) from a limited number of blood samples; and (ii) to explore the relationships between exposure indices to MPA and the clinical status in children with SLE.Methods This was a retrospective study including 36 children with SLE, extracted from the expert system ISBA, for whom full- pharmacokinetic profiles of MPA were collected together with clinical data. A pharmacokinetic model and a BE were developed using an iterative two-stage Bayesian approach. ROC curve analyses and logistic regressions was used to investigate the association of exposure and active disease.ResultsA pharmacokinetic model and a BE were developed that allowed good AUC estimation performance (bias±SD=-0.02±0.15). ROC curve analyses showed that AUC/dose<0.06 and AUC<44 mg*h/L were associated with a good sensitivity and specificity for active disease (78%/94% and 94%/56% respectively). When introduced in a logistic regression model, AUC<44 mg.h/L and AUC/dose<0.06 were associated with an increased risk of active disease (OR=21.2[2.3-196.1], p=0.007; and OR [95%CI]=59.5[5.9-588.2], p=0.0005 respectively).Conclusions The developed pharmacokinetics BE could be used to prospectively test the interest of MPA monitoring for limiting relapse of the disease or its progression.
    British Journal of Clinical Pharmacology 04/2014; 78(4). DOI:10.1111/bcp.12392
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    ABSTRACT: AimsCyclosporine A (CsA) is used in the prophylaxis and treatment of acute and chronic graft-versus-host disease after hematopoietic stem cell (HCT) transplantation. Our objective were to build and compare three independent Bayesian estimators (BE) of CsA area under the curve (AUC) using a limited sampling strategy (LSS), to assist in dose adjustment.Methods The BEs were developed using in parallel: two independent parametric modeling approaches (NONMEM® and iterative two stage (ITS) Bayesian modeling) and the nonparametric adaptive grid method (Pmetrics®). Seventy-two full pharmacokinetic profiles (at pre-dose and 0.33, 0.66, 1, 2, 3, 4, 6, 8 and 12h after dosing) collected from 40 HCT patients given CsA were used to build the pharmacokinetic models, while 15 other profiles (n=7) were kept for validation. For each BE, AUCs estimated using the full profiles were compared to AUCs estimated using 3 samples.ResultsThe pharmacokinetic profiles were well fitted using a two-compartment model with first-order elimination, combined with a gamma function for the absorption phase with ITS and Pmetrics or an Erlang distribution with NONMEM. The derived BE based on a C0-C1h-C4h sampling schedule (best LSS) accurately estimated CsA AUC0-12h in the validation group (n=15; NONMEM: bias (mean ± SD)/RMSE=2.05%±13.31%/13.02%; ITS: 4.61%±10.56%/11.20%; Pmetrics: 0.30%±10.12%/10.47%). The dose chosen confronting the 3 results led to a pertinent dose proposal.ConclusionsBEs developed were all able to predict cyclosporine AUC0-12h in HCT patients using only three blood with minimal bias and may be combined to increase the reliability of CsA dose adjustment in routine.
    British Journal of Clinical Pharmacology 04/2014; 78(4). DOI:10.1111/bcp.12394
  • The Journal of Heart and Lung Transplantation 04/2014; 33(4):S280-S281. DOI:10.1016/j.healun.2014.01.747
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    ABSTRACT: Different associations between single nucleotide polymorphisms (SNPs) in cellular target, metabolism enzymes or transport proteins, and biopsy-proven acute rejection (BPAR) or adverse events have been reported in transplant patients receiving mycophenolate mofetil. This work aimed to study these in patients on enteric-coated mycophenolate sodium (EC-MPS). The study included 189 renal transplant patients from the DOMINOS trial. Fifteen SNPs in IMPDH2, IMPDH1, ABCC2, SLCO1B3, UGT1A8, UGT1A9, UGT2B7, CYP2C8, HUS1, and IL12A were genotyped in all patients. Associations between SNPs and the first event of BPAR or diarrhea were investigated using multivariate logistic regressions. Associations between SNPs and leukopenia or anemia at nine different visits between days 0 and 190 after transplantation were studied using time-dependent Cox proportional hazards regression models. Multivariate analyses showed that the CYP2C8 rs11572076 wild-type genotype was associated significantly with a lower risk of leukopenia [GG vs. GA: hazard ratio (95% confidence interval) 0.14 (0.03, 0.59), P=0.00783]. Higher EC-MPS doses and the UGT2B7 c.-840 G>A variant allele were associated with an increased risk of anemia [EC-MPS per unit dose increase: 1.004 (1.003, 1.005), P<0.0001; UGT2B7 GA vs. AA: 1.65 (1.12, 2.43), P=0.01043; GG vs. AA: 1.88 (1.23, 2.88), P=0.00343]. However, no significant association was found between any of the SNPs studied and diarrhea or BPAR. Two pharmacogenetic associations reported previously with mycophenolate mofetil were found in a population of 189 renal transplant patients treated with EC-MPS.
    Pharmacogenetics and Genomics 03/2014; DOI:10.1097/FPC.0000000000000045
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    ABSTRACT: Blood concentrations of the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus are currently measured to monitor immunosuppression in transplant patients. The measurement of calcineurin (CN) phosphatase activity has been proposed as a complementary pharmacodynamic approach. However, determining CN activity with current methods is not practical. We developed a new method amenable to routine use.METHODS: Using liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM-MS), we quantified CN activity by measuring the dephosphorylation of a synthetic phosphopeptide substrate. A stable isotope analog of the product peptide served as internal standard, and a novel inhibitor cocktail minimized dephosphorylation by other major serine/threonine phosphatases. The assay was used to determine CN activity in peripheral blood mononuclear cells (PBMCs) isolated from 20 CNI-treated kidney transplant patients and 9 healthy volunteers.RESULTS: Linearity was observed from 0.16 to 2.5 μ mol/L of product peptide, with accuracy in the 15% tolerance range. Intraassay and interassay recoveries were 100.6 (9.6) and 100 (7.5), respectively. Michaelis-Menten kinetics for purified CN were Km = 10.7 (1.6) μ mol/L, Vmax = 2.8 (0.3) μ mol/min/mg, and for Jurkat lysate, Km = 182.2 (118.0) μ mol/L, Vmax = 0.013 (0.006) μ mol/min/mg. PBMC CN activity was successfully measured in a single tube with an inhibitor cocktail.CONCLUSIONS: Because LC-MRM-MS is commonly used in routine clinical dosage of drugs, this CN activity assay could be applied, with parallel blood drug concentration monitoring, to a large panel of patients to reevaluate the validity of PBMC CN activity monitoring.
    Clinical Chemistry 11/2013; 60(2). DOI:10.1373/clinchem.2013.213264
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    ABSTRACT: Our goal was to demonstrate the feasibility of pelvic magnetic resonance imaging (MRI) in the ewe. Two ewes underwent a pelvic 3 Tesla MRI scan, under light anesthesia, with T2-weighted fast spin-echo images and T1-weighted spoiled gradient-echo images. Multiplan T1 weighted images were also obtained after the intravenous injection of a contrast product. One ewe was anestrous and the other one had undergone ovarian stimulation. No incident occurred during the examination. Both the uterus (with two horns) and the ovaries were identified. The intensity of the endometrial, myometrial and ovarian signals was similar to that encountered in women. The uterus and ovaries could be enhanced in both cases. Pelvic vasculature was also studied. In the case of hormonal stimulation, the endometrium was thicker, follicular growth was identified and enhancement seemed greater. MRI in the ewe is feasible and could be helpful in experimental gynecologic research, especially in uterus transplantation.
    Journal of Obstetrics and Gynaecology Research 09/2013; DOI:10.1111/jog.12141
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    ABSTRACT: Recent studies have identified new candidate polymorphisms in the genes related to CYP3A activity or calcineurin inhibitor dose requirements in kidney transplant recipients. These genes and polymorphisms are CYP3A4 (cytochrome P450, family 3, subfamily A, polypeptide 4) (rs35599367-C>T; *22); POR [P450 (cytochrome) oxidoreductase] (rs1057868-C>T; *28); and PPARA (peroxisome proliferator-activated receptor alpha) (rs4253728-G>A). We investigated the impact of these polymorphisms on sirolimus (SRL) in vitro hepatic metabolism, SRL trough concentrations (C0), and SRL adverse events in kidney transplant recipients.METHODS: The clinical study included 113 stable kidney transplant patients switched from a calcineurin inhibitor to SRL (SRL C0 measured at 1, 3, and 6 months thereafter). We investigated SRL metabolism in vitro using human liver microsomes derived from individual donors (n = 31). Microsomes and patients were genotyped by use of Taqman® allelic discrimination assays. The effects of polymorphisms and covariates were studied using multilinear regression imbedded in linear mixed-effect models or logistic regressions.RESULTS: In vitro, the CYP3A4*22 allele resulted in approximately 20% lower metabolic rates of SRL (P = 0.0411). No significant association was found between CYP3A4, CYP3A5, or PPARA genotypes and SRL dose, C0, or C0/dose in kidney transplant patients. POR*28 was associated with a minor but significant decrease in SRL log-transformed C0 [CT/TT vs CC, β = -0.15 (0.05); P = 0.0197] but this did not have any impact on the dose administered, which limited the relevance of the finding. After adjustment for nongenetic covariates and correction for false discovery finding, none of the single-nucleotide polymorphisms tested showed significant association with SRL adverse events.CONCLUSIONS: These recently described polymorphisms do not seem to substantially influence the pharmacokinetics of SRL or the occurrence of SRL adverse events in kidney transplant recipients.
    Clinical Chemistry 08/2013; 59(12). DOI:10.1373/clinchem.2013.204990
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    ABSTRACT: OBJECTIVES:: Since 2007, a number of transplantation centers have been routinely using an expert system for tacrolimus (TAC) dose adjustment in kidney allograft recipients, based on PK modeling and Bayesian estimation for area-under-the-curve (AUC) determination. This has allowed the setting up of a large database of TAC pharmacokinetic profiles and AUC values, a part of which was analyzed here. METHODS:: We retrospectively studied 2030 requests posted by 21 different centers for routine TAC dose adjustment in 1000 different adult renal transplant patients (not enrolled in any kind of concentration-controlled clinical trial). For each request, the following information was obtained: time elapsed since transplantation, TAC daily dose, calculated AUC, and trough concentration (C0). RESULTS:: The dose-standardized exposure to TAC significantly and progressively increased in the months after transplantation: from month (M) 1 to M9 C0/dose increased from 2.33 to 3.44 mcg·L·mg and AUC/dose from 43.1 to 64.2 mcg·h·L·mg, respectively. On the contrary, in patients beyond the first year whose C0 or AUC was in the target range, the odds of remaining in this range were high for a long time period, suggesting a low intrapatient variability in the stable phase. Regression analyses showed that the correlation between C0 and AUC was better in the first 3-month period (r² = 0.76) than later on (r² ≤ 0.67). Using the regression equations obtained, AUC ranges corresponding to different applicable C0 targets were calculated. CONCLUSIONS:: From a large number of kidney graft recipients, we have estimated the relationships between C0 and AUC, modeled the evolution of TAC exposure with time and defined AUC targets that could be useful to lead further controlled-concentration trials and improve routine TAC therapeutic drug monitoring.
    Therapeutic drug monitoring 05/2013; DOI:10.1097/FTD.0b013e318285e779
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    ABSTRACT: This study aimed to investigate the association between longitudinal exposure to mycophenolic acid (MPA) and acute rejection (AR) risk in the first year after renal transplantation, and to propose MPA exposure targets conditionally to this association. A joint model, adjusted for monitoring strategy (fixed-dose versus concentration-controlled) and recipient age, was developed; it combined a mixed-effects model to describe the whole pattern of MPA exposure (i.e. area under the concentration-time curve -AUC-) and a survival model. MPA AUC thresholds were determined using time-dependent Receiver-Operating Characteristics (ROC) curves. Data from 490 adult renal-transplant recipients, representative of the general population of adult renal-transplant patients (i.e. including patients considered at low immunological risk-enrolled in the OPERA trial- as well as second renal transplant and patients co-treated by either cyclosporine or tacrolimus), were analyzed. A significant association was found between the longitudinal exposure to MPA (MPA AUCs=f(t)) and AR (p=0.0081), and validated by bootstrapping. A significant positive correlation was observed between time post-transplantation and ROC thresholds which increased in average from 35mg.h/L in the first days to 41mg.h/L beyond six months post-transplantation (p<0.001). Using a new modeling approach which recognizes the repeated measures in a same patient, this study supports the association between MPA exposure and AR.
    Pharmacological Research 04/2013; DOI:10.1016/j.phrs.2013.03.009

Publication Stats

5k Citations
814.15 Total Impact Points


  • 2011–2014
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
    • CHU de Lyon - Hôpital Femme-Mère-Enfant
      Lyons, Rhône-Alpes, France
    • Columbia University
      New York, New York, United States
  • 1997–2014
    • University of Limoges
      • Faculté de Médecine
      Limages, Limousin, France
  • 2007–2013
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2002–2012
    • Centre Hospitalier Universitaire de Limoges
      • Department of Pharmacology, Toxicology and Pharmacovigilance
      Limoges, Limousin, France
  • 2006
    • Université Victor Segalen Bordeaux 2
      • Institut de Santé Publique d'Epidémiologie et de Développement (ISPED)
      Bordeaux, Aquitaine, France
    • University of Santiago de Compostela
      Santiago, Galicia, Spain
  • 2005
    • University of Tours
      Tours, Centre, France