Guillaume Hoizey

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

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Publications (55)131.35 Total impact

  • Therapeutic Drug Monitoring - THER DRUG MONIT. 01/2005; 27(2).
  • Therapeutic Drug Monitoring - THER DRUG MONIT. 01/2005; 27(2).
  • Therapeutic Drug Monitoring - THER DRUG MONIT. 01/2005; 27(2).
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    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.
    Clinical Pharmacokinetics 01/2005; 44(8):837-47. · 5.49 Impact Factor
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    British Journal of Clinical Pharmacology 02/2004; 57(1):115-6. · 3.69 Impact Factor
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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.
    EMC - Toxicologie-Pathologie 01/2004;
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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.
    Journal of Neuro-Oncology 01/2004; 67(1-2):131-8. · 3.12 Impact Factor
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    ABSTRACT: Ethanol is one of the most common toxic agent. Diagnostic of an acute intoxication relies upon patient’medical history and is confirmed by measurement of blood ethanol concentrations. The lack of specific treatment implies close monitoring of the patient until disappearance of clinical symptoms, usually attained in a few hours. This intoxication should be taken seriously due to the rare occurrence of potentially lethal complications.
    EMC - Toxicologie-Pathologie 01/2004; 1(1):2-6.
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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.
    Journal Européen des Urgences 01/2004; 17(4):201-203.
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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.
    Journal of toxicology. Clinical toxicology 02/2003; 41(2):181-3.
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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 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.
    Clinical Toxicology - CLIN TOXICOL. 01/2003; 41(2):181-183.
  • Annales de Toxicologie Analytique 01/2003; 15(4):266-270.
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    British Journal of Clinical Pharmacology 12/2002; 54(5):548. · 3.69 Impact Factor
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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).
    Journal of Pharmaceutical and Biomedical Analysis 10/2002; 30(3):661-6. · 2.95 Impact Factor
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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.
    Clinical Endocrinology 02/2002; 56(1):119-22. · 3.40 Impact Factor
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    ABSTRACT: A nonlethal poisoning case by methyl bromide in a young woman due to leakage of old fire extinguishers is described. The patient developed major action and intention myoclonus the day following exposure. Inorganic bromide concentrations in plasma were determined by inductively coupled plasma mass spectrometry. The initial plasma bromide level was 202 mg/L, 40-fold in excess than the commonly accepted tolerance limit, and decreased slowly to normal levels within 2 months. Although plasma inorganic bromide concentration is known not to be directly correlated to the severity of organic bromide poisoning, its determination was, in the present case, particularly useful to confirm the diagnosis. One year post-exposure, the patient showed no sign of central nervous system toxicity. While such a case of poisoning is particularly rare today, it illustrates, however, that the danger still exists in France although the destruction
    Journal of toxicology. Clinical toxicology 02/2002; 40(6):817-21.
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    ABSTRACT: Le méthylphénidate (Ritaline?) est le seul psychostimulant utilisé en France et indiqué dans le traitement du déficit de l'attention avec hyperactivité chez l'enfant de plus de 6 ans. Il est soumis à des conditions de prescription et de délivrance particulières. A ce titre, il requiert notamment une prescription initiale hospitalière d'un spécialiste en neurologie, psychiatrie ou pédiatrie et appartient à la liste des stupéfiants. Les effets secondaires notifiés dans la Banque fran¸aise de Pharmacovigilance, depuis sa mise sur le marché en 1995, ont été analysés. 21 événements indésirables ont été rapportés. Dans 16 cas, le méthylphénidate était suspect. Ils sont généralement de gravité moyenne et dans la plupart des cas d'évolution rapidement favorable. Les résultats ne suggèrent pas, en France, l'émergence d'un mésusage ou d'un usage abusif du méthylphénidate pour une population d'environ 1300 à 4000 enfants traités, à ce jour. Dans l'attente d'information supplémentaire concernant les effets à long terme du méthylphénidate, et afin de limiter tout risque de mésusage, d'utilisation inappropriée ou exagérée, les conditions actuelles de prescription et de délivrance en vigueur doivent être maintenues en France, et pourraient être développées dans d'autres pays.
    Thérapie 12/2001; 57(2):189-193. · 0.37 Impact Factor
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    ABSTRACT: The purpose of this study was to determine the pharmacokinetics of gacyclidine, a non-competitive NMDA antagonist, in plasma and spinal cord extracellular fluid (ECF) after IV administration of single enantiomers in rats. After implantation of microdialysis probes in spinal cord, concentrations in plasma and ECF dialysates were determined by a chiral GC/MS assay over 5 h after administration of either (+)-gacyclidine or (-)-gacyclidine (1.25 mg/kg). Plasma protein binding was estimated in vitro by equilibrium dialysis. Plasma concentrations decayed in parallel in a biphasic manner (t(1/2)alpha approximately 9 min; t(1/2)beta approximately 90 min) with no significant difference between the two enantiomers. Clearance of (+)-gacyclidine and (-)-gacyclidine (291 versus 275 ml/min per kg, respectively), volume of distribution (Vdbeta: 38 versus 40 l/kg), and protein binding (90 versus 89%) were not stereoselective. Both gacyclidine enantiomers were quantifiable in spinal cord ECF 10 min after drug administration and their concentrations remained stable over the duration of the experiment in spite of changing blood concentrations. Penetration of the two enantiomers in spinal cord ECF was similar although highly variable between animals. Exposure of spinal cord ECF was comparable for both enantiomers, and not correlated with plasma AUCs. This study showed the absence of any pharmacokinetic difference between the two enantiomers when administered individually, and no enantiomeric inversion. Both gacyclidine enantiomers penetrate rapidly and extensively into spinal cord ECF, and their distribution may involve an active transport system.
    International Journal of Pharmaceutics 11/2001; 229(1-2):147-53. · 3.99 Impact Factor
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    T Trenque, G Hoizey, D Lamiable
    Diabetes Care 04/2001; 24(4):792-3. · 7.74 Impact Factor
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    ABSTRACT: The pharmacokinetics of gacyclidine enantiomers, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, were studied in plasma and spinal cord extracellular fluid (ECF) after experimental spinal cord injury in rats. Spinal cord trauma was produced by introducing an inflatable balloon in the dorsal subdural space. Upon implantation of microdialysis probes in spinal cord (T9) and intravenous (iv) bolus administration of (+/-)-gacyclidine (2.5 mg/kg), concentrations in plasma and ECF were monitored over 5 h and analyzed by a stereospecific gas chromatography-mass spectrometry (GC-MS) assay. In plasma, concentrations of (+)-gacyclidine were approximately 25% higher than those of (-)-gacyclidine over the duration of the experiment and decayed in parallel (t(1/2 alpha) approximately 7 min; t(1/2 beta) approximately 90 min) with no significant difference between the two enantiomers. Clearance (CL) and volume of distribution (Vd) of (-)-gacyclidine were approximately 20% higher than those of its optical antipode (CL: 285 versus 236 mL. kg(-1). min(-1); Vd(beta): 39.3 versus 31.2 l/kg). Protein binding (approximately 91%) was not stereoselective. In spinal cord ECF, both enantiomers were quantifiable within 10 min after drug administration, and their concentration remained stable over the duration of the experiment in spite of changing blood concentrations. Repeated iv bolus injections of gacyclidine did not modify these profiles. Areas under the curves (AUCs) of concentration in ECF versus time were similar for both enantiomers and not correlated with AUCs in plasma. Penetration of (-)-gacyclidine was, however, significantly higher (approximately 30%) than that of (+)-gacyclidine. In summary, the disposition of gacyclidine enantiomers is stereoselective. Both enantiomers exhibit a high affinity for spinal cord tissue, and the drug exchange between plasma and spinal cord ECF involves an active transport system. These findings contribute to the explanation of the discrepancy between drug concentrations in plasma and spinal cord ECF.
    Journal of Pharmaceutical Sciences 02/2001; 90(1):70-8. · 3.13 Impact Factor

Publication Stats

409 Citations
131.35 Total Impact Points

Institutions

  • 2002–2009
    • Centre Hospitalier Universitaire de Reims
      • Laboratoire de Pharmacologie - Toxicologie
      Reims, Champagne-Ardenne, France
    • Hôpital Universitaire Robert Debré
      Lutetia Parisorum, Île-de-France, France
  • 1999–2007
    • Université de Reims Champagne-Ardenne
      • UFR de Pharmacie
      Rheims, Champagne-Ardenne, France
  • 2006
    • Centre Hospitalier Universitaire de Limoges
      Limages, Limousin, France
  • 2005–2006
    • University of Limoges
      • Faculté de Médecine
      Limages, Limousin, France