Guillaume Hoizey

Centre Hospitalier Universitaire de Reims, Rheims, Champagne-Ardenne, France

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Publications (60)143.01 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Mycophenolic acid (MPA) shows complex plasma concentration-time profiles, particularly in the immediate (first month) post-transplantation phase for which no relevant pharmacokinetic model has been proposed thus far. The aim of this study was to develop a model to accurately describe the time profile of plasma MPA concentrations after oral administration of mycophenolate mofetil in adult kidney transplant patients, in any post-transplantation period. Full interdose pharmacokinetic profiles were collected in 45 adult renal transplant patients who were orally administered mycophenolate mofetil and ciclosporin; 25 patients were de novo transplant patients for whom individual pharmacokinetics were assessed at three post-transplantation periods (days 3, 7 and 30) and 20 patients were stable transplant patients (>3 months post-transplantation). MPA was determined in plasma by liquid chromatography-mass spectrometry. Models combining a single- or double-input (described as single or double gamma distributions) with one- or two-compartments were developed using in-house software and fitted to the individual profiles by nonlinear regression. Visual inspection of the pharmacokinetic profiles showed highly variable absorption profiles and secondary peaks of various intensity. The pharmacokinetic models including a double gamma distribution best fitted these various profiles in the immediate post-transplantation period (mean bias and precision of -0.92% and 20.19%; -1.5% and 18.02%, on day 7 and day 30, respectively), while in the stable post-grafting phase (beyond 3 months), the single- and double-absorption models performed similarly (mean bias and precision of -3.37% and 17.64%; -3.12% and 18.44%, on day 7 and day 30, respectively). The proposed pharmacokinetic models adequately describe the concentration-time profiles of MPA in renal transplant patients and could be helpful in the development of tools for MPA monitoring.
    No preview · Article · Aug 2005 · Clinical Pharmacokinetics
  • Arnaud Robinet · Guillaume Hoizey · Hervé Millart
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    ABSTRACT: Using an isolated non-working rat heart model, this study investigated the mechanisms of pharmacological preconditioning (PC) induced by transient beta1-adrenoreceptor (beta1-AR) stimulation with xamoterol (XA). After 6-hydroxydopamine (6-OHDA) pretreatment and a 20-min stabilization period, hearts were perfused at constant pressure for 20 min then subjected to 40 min of global ischemia and 30 min of reperfusion (I/R, Ctrl); exposed to 0.01 microM XA for 5 min with or without 10 microM atenolol (ATE), a specific antagonist of beta1-AR, followed by a 15-min XA-free perfusion before I/R (PC, ATE-PC, respectively); treated during 20 min with either phosphoinositide (PI) 3-kinase inhibitors, LY-294002 (LY, 15 microM), or wortmaninn (WO, 0.1 microM); protein kinase C (PKC) inhibitor, GF-109203X (GF, 4 nM); or protein kinase A (PKA) inhibitor, H89 (H89, 1 microM), with an infusion starting 3 min before XA (LY-PC, WO-PC, GF-PC, and H89-PC, respectively). The main endpoints were the mean coronary flow (MCF), the left ventricular end-diastolic pressure (LVEDP), rate-pressure product (RPP), and creatine kinase (CK) release. XA induced an increase in the MCF after I/R (t 105 min) and a protective effect on the LVEDP, which were blocked by ATE and abolished with the different inhibitors. The transient increase in RPP following XA infusion was blocked by ATE and was not modified by the inhibitors except for H89. Recovery of RPP, measured 25 min after reperfusion, was improved by XA, blocked by ATE, and decreased with the different inhibitors. Fifteen minutes after the end of ischemia, CK release reached maximal values in all groups. XA provided significant protection whereas ATE and the four inhibitors suppressed XA-induced protection. The transient preischemic exposure to nanomolar concentrations of a beta1-AR agonist is protective against I/R. PI 3-kinase, PKC, and PKA are implicated in the trigger phase of PC. These observations were confirmed by Western blots.
    No preview · Article · Jul 2005 · Cardiovascular Research
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    ABSTRACT: The aim of this study was to develop maximum a posteriori probability (MAP) Bayesian estimators of mycophenolic acid (MPA) pharmacokinetics (PK) capable of accurately estimating the MPA interdose AUC in renal transplant patients using a limited number of blood samples. The individual MPA plasma concentration-time profiles of 44 adult kidney transplant recipients were retrospectively studied: in 24 de novo transplant patients, 2 profiles were obtained on day 7 and day 30 after transplantation, and in 20 stable transplant patients, 1 profile was obtained in the stable period (>3 months). MPA was assayed by liquid chromatography-mass spectrometry. Concentration data were fitted using previously designed PK models, including 1 or 2Gamma-distribution to describe the absorption rate. MAP-Bayesian estimations were performed using an in-house program. For each posttransplantation period, the limited sampling strategies (LSS) providing either the best determination coefficient or the lowest bias for AUC estimates with respect to trapezoidal AUCs were selected and compared with respect to the percentage of "clinically acceptable" AUC estimates (ie, within -20% to +20% of the true value) they yielded. A common LSS (blood samples collected at T20 min, T1 h, and T3 h postdosing), convenient for all 3 periods, was also selected and validated: bias (RMSE%) values were -5.7% (20.5%), -8.2% (14.4%), and +0.4% (12.0%) on D7, D30, and for >M3 with respect to the reference values obtained using the trapezoidal rule, respectively. For the first time, MAP-Bayesian estimators of MPA systemic exposure at different posttransplantation periods (early as well as later periods) could be designed. They have since been used for MPA dose adaptation in concentration-controlled studies as well as for MPA therapeutic drug monitoring in clinical practice.
    No preview · Article · Jun 2005 · Therapeutic Drug Monitoring

  • No preview · Article · Apr 2005 · Therapeutic Drug Monitoring
  • N Djebli · MeurY Le · O Toupance · G Hoizey · A Rousseau · P Marquet

    No preview · Article · Apr 2005 · Therapeutic Drug Monitoring

  • No preview · Article · Apr 2005 · Therapeutic Drug Monitoring
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    ABSTRACT: The safety of new-generation anti-depressants, serotonin re-uptake inhibitors (SSRIs), has improved over tricyclic anti-depressants. Adverse effects are limited (lower affinity for histaminic, adrenergic and muscarinic receptors), especially when prescribed for elderly patients. Adverse effects include induced severe hyponatremia causing neurological disorders related to inappropriate ADH secretion.
    No preview · Article · Dec 2004 · JEUR
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    ABSTRACT: The safety of new-generation anti-depressants, serotonin re-uptake inhibitors (SSRIs), has improved over tricyclic anti-depressants.Adverse effects are limited (lower affinity for histaminic, adrenergic and muscarinic receptors), especially when prescribed for elderly patients.Adverse effects include induced severe hyponatremia causing neurological disorders related to inappropriate ADH secretion.
    No preview · Article · Oct 2004 · Journal Européen des Urgences
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    ABSTRACT: Comparison of the influence of two different brain tumors (C6 and CNS1 glioma) on methotrexate (MTX) disposition in plasma, brain, and tumor tissue extracellular fluid (ECF). Serial collection of plasma samples and brain ECF dialysates after i.v. bolus administration of MTX (50 mg kg(-1)) for 4 h. Quantitation of MTX concentrations by HPLC-UV. Histological studies revealed a 3-fold higher number of blood vessels in CNS1 than in C6 tumor tissue. In vivo recoveries (reverse dialysis) were significantly different in tumor tissue (C6: 8.0 +/- 3.8%; CNS1: 4.9 +/- 2.5%), and in the contralateral hemisphere (C6: 6.0 +/- 4.0%; CNS1: 3.9 +/- 2.5%) between the two tumors. Area under the concentration-time curve (AUC) in plasma was 30% higher in CNS1 than in C6 due to a lower systemic clearance. Maximum MTX levels in brain tumor ECF were significantly higher in CNS1 than in C6, and decreased faster in CNS1 than in C6 tumor-bearing rats. Penetration in tumor ECF (AUC(ECF)/AUC(Plasma) ratio) was similar in CNS1 and C6. MTX concentrations in contralateral hemisphere were significantly lower than in tumor tissue and dependent on tumor model. C6 and CNS1 brain tumors have a distinct yet highly variable impact on MTX penetration in brain and brain tumor ECF.
    Full-text · Article · Mar 2004 · Journal of Neuro-Oncology
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    C Frances · G Hoizey · H Millart · T Trenque

    Full-text · Article · Feb 2004 · British Journal of Clinical Pharmacology
  • Denis Lamiable · Guillaume Hoizey · Hélène Marty · Richard Vistelle
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    ABSTRACT: Methanol is an alcohol frequently used as a solvent in the industry, and as an antifreeze and cleaning agent for domestic use. Weakly toxic by itself, its main metabolite (formic acid) induces severe ocular and neurological toxicities. The diagnostic of an intoxication is based on the coexistence of acidosis with increased anion gap and osmolar gap coupled with the presence of methanol in blood. Treatment involves alcalinization, administration of inhibitors of methanol metabolism (ethanol, 4-methylpyrazole) and hemodialysis for severe cases.
    No preview · Article · Jan 2004 · EMC - Toxicologie-Pathologie
  • D Lamiable · G Hoizey · H Marty · R Vistelle
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    ABSTRACT: L’éthanol, ou alcool éthylique, est une des substances les plus souvent impliquées dans les intoxications aiguës. Le diagnostic repose essentiellement sur l’anamnèse et est confirmé par détermination de l’éthanolémie. En l’absence de traitement spécifique, celui-ci repose essentiellement sur la surveillance du patient jusqu’à disparition des symptômes, qui régressent généralement en quelques heures. Cette intoxication ne doit pas être banalisée car elle expose le patient à des complications rares mais pouvant engager le pronostic vital.
    No preview · Article · Jan 2004 · EMC - Toxicologie-Pathologie
  • D. Lamiable · G. Hoizey · H. Marty · R. Vistelle
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    ABSTRACT: Methanol is an alcohol frequently used as a solvent in the industry, and as an antifreeze and cleaning agent for domestic use. Weakly toxic by itself, its main metabolite (formic acid) induces severe ocular and neurological toxicities. The diagnostic of an intoxication is based on the coexistence of acidosis with increased anion gap and osmolar gap coupled with the presence of methanol in blood. Treatment involves alcalinization, administration of inhibitors of methanol metabolism (ethanol, 4-methylpyrazole) and hemodialysis for severe cases.
    No preview · Article · Jan 2004 · EMC - Toxicologie-Pathologie
  • C Frances · G Hoizey · D Lamiable · H Millart · T Trenque
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    ABSTRACT: Bromide intoxication today is an infrequent disease, but preparations containing bromide are still available in nonprescription compounds, on the French market. We report a casewith bromide intoxication due to daily over intake (approximately 20 tablets per day; i.e. total elemental bromide intake approximately 6 g/day) of calcium bromo-galactogluconate (Calcibronat) for 1.5 months. A 30-year-old woman with a long history of psychotropic drug abuse was hospitalized in a psychiatric department for neuropsychological manifestations. She presented a seriously disturbed mental status with confusion, disorientation, auditory and visual hallucinations, and loss of short-time memory. A markedly increased serum bromide level of 1717 mg/L (21.5 mEq/L) measured on the first day after her admission confirmed the diagnosis of chronic bromism suspected based on her symptomatology. During her hospitalization, bromide plasma concentrations were measured and monitored using inductively coupled plasma mass spectrometry, a sensitive and very specific method. After withdrawal of the drug, the symptoms improved within 8 days. Serial bromide concentrations gradually declined throughout nearly 2 months of monitoring, until she was discharged from the hospital. We found an elimination half-life of bromide in blood of approximately of 10 days. This case demonstrates that, while today bromism occurs infrequently, it should still be included in the differential diagnosis of neuropsychiatric symptoms.
    No preview · Article · Feb 2003 · Journal of toxicology. Clinical toxicology

  • No preview · Article · Jan 2003 · Annales de Toxicologie Analytique
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bromide intoxication today is an infrequent disease, but preparations containing bromide are still available in nonprescription compounds, on the French market. We report a case with bromide intoxication due to daily over intake (20 tablets per day; i.e. total elemental bromide intake 6 g/day) of calcium bromo-galactogluconate (Calcibronat®) for 1.5 months. A 30-year-old woman with a long history of psychotropic drug abuse was hospitalized in a psychiatric department for neuropsychological manifestations. She presented a seriously disturbed mental status with confusion, disorientation, auditory and visual hallucinations, and loss of short-time memory. A markedly increased serum bromide level of 1717 mg/L (21.5 mEq/L) measured on the first day after her admission confirmed the diagnosis of chronic bromism suspected based on her symptomatology. During her hospitalization, bromide plasma concentrations were measured and monitored using inductively coupled plasma mass spectrometry, a sensitive and very specific method. After withdrawal of the drug, the symptoms improved within 8 days. Serial bromide concentrations gradually declined throughout nearly 2 months of monitoring, until she was discharged from the hospital. We found an elimination half-life of bromide in blood of approximately of 10 days. This case demonstrates that, while today bromism occurs infrequently, it should still be included in the differential diagnosis of neuropsychiatric symptoms.
    No preview · Article · Jan 2003 · Clinical Toxicology
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    T Trenque · C Frances · H Millart · G Hoizey · M L Germain

    Full-text · Article · Dec 2002 · British Journal of Clinical Pharmacology
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    ABSTRACT: A simple and accurate high-performance liquid chromatographic method with ultraviolet detection at 220 nm has been validated for the simultaneous determination of amoxicillin and clavulanic acid in human plasma. Plasma samples were pretreated by direct deproteinization with methanol. A good chromatographic separation between both compounds was achieved using a reversed phase C8 column and a mobile phase, consisting of acetonitrile-phosphate solution-tetramethyl ammonium chloride solution. The calibration curves were linear over the concentration range of 0.625-20 mg l(-1) for amoxicillin and 0.3125-10 mg l(-1) for clavulanic acid with determination coefficients > 0.998. The method is accurate (bias < 7%) and reproducible (intra- and inter-day R.S.D. < 15%), with a quantitation limit of 0.625 and 0.3125 mg l(-1) for amoxicillin and clavulanic acid, respectively. Analytical recoveries from human plasma ranged from 91 to 102% for both components. This fully validated method, which allows the simultaneous measurement of amoxicillin and clavulanic acid in biological samples, is rapid (total run time < 10 min) and requires only a 100 microl sample. This assay is suitable for biomedical applications and was successfully applied to a pilot pharmacokinetics study in healthy volunteers after a single-oral administration of amoxicillin/clavulanic acid combination (500/125 mg).
    No preview · Article · Oct 2002 · Journal of Pharmaceutical and Biomedical Analysis
  • C. Frances · G. Hoizey · H. Millart · T. Trenque
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    ABSTRACT: Methylphenidate (Ritalin®) is the only psychostimulant approved in France and indicated in attention deficit hyperactivity disorder in children over 6 years. It is under restricted prescription and distribution conditions. As such, it requires a hospital initiated prescription from either a neurology, psychiatry or pediatric specialist and it is covered by the « narcotics » schedule. The French Pharmacovigilance database spontaneous adverse drug reactions reporting, since it was approved in 1995, were analyzed. 21 adverse drug reactions were reported. In 16 cases, methylphenidate was suspected. They were generally non-serious, mild side effects and in most cases promptly resolved. These results do not suggest methylphenidate misuse in France or an overuse in between 1300 and 4000 treated children, to date. Until more information is available concerning the long-term effects of methylphenidate, and in order to limit misuse, inappropriate or overuse, the current prescription and dispensing regulation should be maintained in France, and could well be developed in other countries.
    No preview · Article · Mar 2002 · Thérapie
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    ABSTRACT: We studied the diurnal fluctuations of plasma concentrations of methoxyamines (metanephrine and normetanephrine) and of their parent amines (epinephrine and norepinephrine) in normotensive subjects. Serial blood sampling at 09.00 h, 11.00 h, 12.00 h, 14.00 h, 16.00 h, 18.00 h and 20.00 h in 28 healthy volunteers at rest. Determination of plasma concentrations of free catecholamines and total methoxyamines (free and sulpho-conjugates) was carried out by high-performance liquid chromatography with electrochemical detection. Mean (+/- SD) plasma concentrations of total metanephrine (MN) and normetanephrine (NMN) were 4.31 +/- 1.73 nmol/l (range: 0.96-9.3 nmol/l) and 8.13 +/- 2.54 nmol/l (range: 3.14-17.0 nmol/l), respectively. The NMN/MN ratio ranged between 0.8 and 7.8 (mean +/- SD 2.1 +/- 1.0). Mean plasma concentrations of free epinephrine and norepinephrine were 0.21 +/- 0.12 nmol/l (range: 0.06-1.39 nmol/l) and 1.61 +/- 0.62 nmol/l (range: 0.47-4.01 nmol/l), respectively. Despite marked intraindividual fluctuations, mean methoxyamine and catecholamine levels remained constant over the entire duration of the experiment. The absence of fluctuations of plasma levels of total methoxyamines suggests that their measurement could be carried out at any time within the diurnal time frame. Further investigations, however, remain necessary to validate these findings in patients with hypertension and/or pheochromocytoma, and to explain the ever important intraindividual variation in plasma concentrations of methoxyamines and of their parent compounds.
    No preview · Article · Feb 2002 · Clinical Endocrinology

Publication Stats

645 Citations
143.01 Total Impact Points

Institutions

  • 2010
    • Centre Hospitalier Universitaire de Reims
      • Laboratoire de Pharmacologie - Toxicologie
      Rheims, Champagne-Ardenne, France
  • 2009
    • Hôpital Universitaire Robert Debré
      Lutetia Parisorum, Île-de-France, France
  • 1999-2004
    • Université de Reims Champagne-Ardenne
      • UFR de Pharmacie
      Rheims, Champagne-Ardenne, France