Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Michel Ducher is active.

Publication


Featured researches published by Michel Ducher.


Fundamental & Clinical Pharmacology | 2008

The Hill equation: a review of its capabilities in pharmacological modelling.

Sylvain Goutelle; Michel Maurin; Florent Rougier; Xavier Barbaut; Laurent Bourguignon; Michel Ducher; Pascal Maire

The Hill equation was first introduced by A.V. Hill to describe the equilibrium relationship between oxygen tension and the saturation of haemoglobin. In pharmacology, the Hill equation has been extensively used to analyse quantitative drug–receptor relationships. Many pharmacokinetic–pharmacodynamic models have used the Hill equation to describe nonlinear drug dose–response relationships. Although the Hill equation is widely used, its many properties are not all well known. This article aims at reviewing the various properties of the Hill equation. The descriptive aspects of the Hill equation, in particular mathematical and graphical properties, are examined, and related to Hill’s original work. The mechanistic aspect of the Hill equation, involving a strong connection with the Guldberg and Waage law of mass action, is also described. Finally, a probabilistic view of the Hill equation is examined. Here, we provide some new calculation results, such as Fisher information and Shannon entropy, and we introduce multivariate probabilistic Hill equations. The main features and potential applications of this probabilistic approach are also discussed. Thus, within the same formalism, the Hill equation has many different properties which can be of great interest for those interested in mathematical modelling in pharmacology and biosciences.


Antimicrobial Agents and Chemotherapy | 2003

Aminoglycoside Nephrotoxicity: Modeling, Simulation, and Control

Florent Rougier; Daniel Claude; Michel Maurin; Alexandre Sedoglavic; Michel Ducher; Stéphane Corvaisier; Roger W. Jelliffe; Pascal Maire

ABSTRACT The main constraints on the administration of aminoglycosides are the risks of nephrotoxicity and ototoxicity, which can lead to acute, renal, vestibular, and auditory toxicities. In the present study we focused on nephrotoxicity. No reliable predictor of nephrotoxicity has been found to date. We have developed a deterministic model which describes the pharmacokinetic behavior of aminoglycosides (with a two-compartment model), the kinetics of aminoglycoside accumulation in the renal cortex, the effects of aminoglycosides on renal cells, the resulting effects on renal function by tubuloglomerular feedback, and the resulting effects on serum creatinine concentrations. The pharmacokinetic parameter values were estimated by use of the NPEM program. The estimated pharmacodynamic parameter values were obtained after minimization of the least-squares objective function between the measured and the calculated serum creatinine concentrations. A simulation program assessed the influences of the dosage regimens on the occurrence of nephrotoxicity. We have also demonstrated the relevancy of modeling of the circadian rhythm of the renal function. We have shown the ability of the model to fit with 49 observed serum creatinine concentrations for a group of eight patients treated for endocarditis by comparison with 49 calculated serum creatinine concentrations (r2 = 0.988; P < 0.001). We have found that for the same daily dose, the nephrotoxicity observed with a thrice-daily administration schedule appears more rapidly, induces a greater decrease in renal function, and is more prolonged than those that occur with less frequent administration schedules (for example, once-daily administration). Moreover, for once-daily administration, we have demonstrated that the time of day of administration can influence the incidence of aminoglycoside nephrotoxicity. The lowest level of nephrotoxicity was observed when aminoglycosides were administered at 1:30 p.m. Clinical application of this model might make it possible to adjust aminoglycoside dosage regimens by taking into account both the efficacies and toxicities of the drugs.


Hypertension | 2001

Perceived Job Stress but not Individual Cardiovascular Reactivity to Stress Is Related to Higher Blood Pressure at Work

Jean Pierre Fauvel; Pierre Quelin; Michel Ducher; Hantanirina Rakotomalala; M. Laville

Abstract—Psychological stress has been reported to be related to higher blood pressure (BP) and unfavorable cardiovascular profile. However, because of the complexity of personal stress management, a multilevel stress measurement strategy is needed. The aim of this cross-sectional study was to analyze the respective influences of the subjective perception of professional strain (high demand and low latitude) and cardiovascular reactivity to a stress test (Stroop stress test) on BP. Worksite BP was measured in 303 healthy normotensive subjects, 18 to 55 years of age, who worked in the same chemical company. In a subset of 70 randomly selected subjects, 24-hour ambulatory BP was performed to assess BP during working hours. The 20% of subjects who reported the highest job strain (high-strain group) or the highest BP stress reactivity (high-responder group) were compared with the remaining subjects (80%) (non-high-strain or low-responder groups). Subjects who submitted to the highest job strain had significantly higher ambulatory diastolic BP (4.5 mm Hg, P =0.015) during only working hours, whereas BP was similar during the remaining hours. Worksite BP and stress cardiovascular reactivity were similar between job strain groups. BP stress reactivity did not influence worksite and ambulatory BP. Spontaneous BP variability assessed by standard deviation and spectral analysis was equivalent between complementary groups. Prevalence of microalbuminuria was significantly higher in the high-responder group (8.2% versus 2.5% in low responders) and only slightly higher in the high-strain group (6.2% versus 3.2% in non-high strain). Potential confounding factors, such as age, gender, alcohol consumption, salt intake, body mass index, and occupation, which were equivalent between groups, did not interfere with our results. Our study quantifies high-professional strain effects on BP levels that appear to be higher only during the working period and to be independent from spontaneous BP variability and stress BP reactivity.


Transplantation | 2011

Estimating glomerular filtration rate in kidney transplant recipients: performance over time of four creatinine-based formulas.

Fanny Buron; Aoumer Hadj-Aissa; Laurence Dubourg; Emmanuel Morelon; Jean-Paul Steghens; Michel Ducher; Jean-Pierre Fauvel

Background. The management of kidney transplant recipients requires accurate estimate of glomerular filtration rate (GFR). This study aims at evaluating the performance of four creatinine-based formulas for estimating the GFR (estimated GFR) in this population. Methods. Performances of Cockcroft and Gault formula, Modification of Diet in Renal Disease (MDRD) simplified formula, Chronic Kidney Disease Epidemiology Collaboration formula, and Nankivell formula were assessed compared with inulin clearance taken as the gold standard for measuring GFR (measured GFR). Performances were assessed using the first measurements of GFR obtained in 1249 subjects. How estimated GFR tracks changes in measured GFR over time since transplantation in those patients with repeated measures was also assessed. Results. The MDRD formula provided the best estimate of GFR with a mean bias of −0.5 mL/min/1.73 m2, a standard deviation of bias of 12 mL/min/1.73 m2, and a 30% accuracy at 85%. The MDRD formula also seemed to provide the best performance for estimating GFR, irrespective of age, stage of renal failure, and in people whose body mass index was more than 18.5 kg/m2. This robustness is important in clinical practice. The performance of the four formulas was not modified by the posttransplant period. Conclusion. Even if 30% accuracy was suboptimal in the Kidney Disease Outcomes Quality Initiative guidelines, our results, obtained in a large number of patients, lead us to recommend using the MDRD formula to monitor GFR in kidney transplant recipients.


Hypertension | 2000

Mental Stress–Induced Increase in Blood Pressure Is Not Related to Baroreflex Sensitivity in Middle-Aged Healthy Men

Jean Pierre Fauvel; Catherine Cerutti; Pierre Quelin; M. Laville; Marie Paule Gustin; Christian Paultre; Michel Ducher

The baroreflex that acts to blunt blood pressure (BP) variations through opposite variations in heart rate should limit the BP increase produced by an emotional challenge. However, relations between baroreflex sensitivity and BP reactivity induced by a psychological stress in a large group of adults have never been firmly established. In 280 healthy men, rest (10 minutes) and stress (5 minutes) BP and heart rate were recorded beat to beat by a blood pressure monitor. The mental stress was elicited by a well-standardized computerized version of a word color conflict stress test (Stroop Color Test). Rest and stress baroreflex sensitivity was assessed by the cross-spectral analysis of BP and heart rate and by the sequence method. The stress-induced increase in systolic BP (22.4+/-0.1 mm Hg) was not correlated with resting baroreflex sensitivity but was slightly correlated (r=0.2, P<0.001) with BP variability assessed either by standard deviation or by mid-frequency band spectral power. Our results suggested that a centrally mediated sympathetic stimulation overcame cardiac autonomic regulation and emphasized the role of the sympathetic vasoconstriction in the pressure response at the onset of the stressing stimulation. During the sustained sympathoexcitatory phase, the cardiac baroreflex blunts BP variations but at a lower sensitivity.


Clinical Pharmacokinectics | 2003

AMINOGLYCOSIDE DOSAGES AND NEPHROTOXICITY: QUANTITATIVE RELATIONSHIPS

Florent Rougier; Michel Ducher; Michel Maurin; Stéphane Corvaisier; Daniel Claude; Roger W. Jelliffe; Pascal Maire

ObjectiveTo develop a model that relates the probability of occurrence of nephrotoxicity to the cumulative area under the curve (AUC) of amikacin serum concentration.Design and patientsThis was a retrospective study of two groups of patients in whom nephrotoxicity was observed after administration of amikacin. The first group consisted of patients treated with once-daily administration (ODA) [n = 13]. The second group consisted of patients treated with twice-daily administration (TDA) [n = 22].Main outcome measureThe probability of nephrotoxicity occurrence.ResultsThe model is a powerful tool to represent and describe the influence of the dosage regimen on aminoglycoside nephrotoxicity. The onset of nephrotoxicity is delayed in the ODA group (p = 0.01) for the same total daily dose among the two groups. The cumulative serum AUC values at onset of nephrotoxicity were greater for the ODA group (p = 0.029). In addition, for the same probability of nephrotoxicity occurrence (50%), the cumulative AUC for the ODA dosage regimen is 2 613 mg · h/L versus only 1 521 mg · h/L for the TDA dosage regimen. The difference in nephrotoxicity between ODA and TDA is greatest for a cumulative AUC of 2 495 mg · h/L, which corresponds to standard therapy with amikacin 900 mg/day during a 7-day period, i.e. 15 mg/kg/day for a 60kg patient with normal renal function (initial creatinine clearance >80 mL/min). For an AUC above 2 495 mg · h/L, the difference in nephrotoxicity decreases slowly to zero. This result means that ODA is especially justified when the treatment is administered over a short duration, i.e. less than 7 days.ConclusionsThe utility of selecting ODA in order to obtain less nephrotoxicity in comparison with TDA is therefore not established when the treatment is prolonged. In clinical use, the choice of the dosage regimen is not clear-cut, and both expected efficacy and expected toxicity must be taken into account in order to obtain an overall optimisation of each patient’s therapy.


Clinical Pharmacokinectics | 2001

Renal Elimination of Amikacin and the Aging Process

Michel Ducher; Pascal Maire; Catherine Cerutti; Yann Bourhis; Fréderic Foltz; Pernille Sorensen; Roger W. Jelliffe; Jean-Pierre Fauvel

ObjectiveAlthough amikacin is primarily eliminated via glomerular filtration, drug concentrations are not consistently predicted in all patients. To better describe the relationship between amikacin clearance and both age and renal function, we used a new heuristic approach involving statistical analysis of dependence.Design and settingRetrospective pharmacokinetic study using data from seven centres in France.Participants634 patients with sepsis aged between 18 and 98 years of age who received intravenous amikacin.MethodsClearance of amikacin was modelled using the NonParametric EM algorithm for a two-compartment model (NPEM2) with intravenous infusion.ResultsA total of 2499 serum amikacin determinations was available for analysis. The relationship between the clearance of amikacin and age was weak. Interestingly, the Z method, which filters data based on dependence criteria, selected data that were best fitted by a polynomial function (r = 0.90; p < 0.001). This representation of the polynomial function was similar to a previously proposed theoretical model describing covariations between the clearance of amikacin and age. However, the polynomial function applied to only 33% of the patients that were selected by the Z method. The correlation between the clearance of amikacin and renal function was also relatively low (r = 0.39). The Z method exhibited a continuous and strong dependence pattern between the clearance of amikacin and age for 49% of the patients.ConclusionsThe Z methodology, which filters data using dependence criteria, confirms that age, renal function and amikacin clearance are strongly related, but only in less than half of a large sample of patients with sepsis without renal pathology. These results suggest that other variables should be taken into account in order to improve the description of the behaviour of amikacin. The Z methodology improved the classical description of relationships between variables, and should be applied to better select pertinent variables in pharmacokinetic studies.


American Journal of Physiology-regulatory Integrative and Comparative Physiology | 1998

Mechanisms of spontaneous baroreflex impairment in Lyon hypertensive rats

Pierre Lantelme; Catherine Cerutti; Ming Lo; Christian Paultre; Michel Ducher

This experiment aimed at 1) comparing the spontaneous baroreflex sensitivity (SBRS) in Lyon genetically hypertensive (LH), normotensive (LN), and low blood pressure (LL) rats and 2) assessing some aspects of the mechanisms of its impairment in LH rats. Baroreflex was studied in control animals after an early chronic converting enzyme inhibition with perindopril and after a 4-wk infusion of ANG II in perindopril-treated rats. The SBRS was determined with a previously validated method, using statistical dependence between blood pressure (BP) and heart rate values recorded in freely moving animals. LH rats exhibited high BP, cardiac hypertrophy, and decreased SBRS (LH, 1.3 ± 0.2; LN, 2.5 ± 0.4; LL, 2.2 ± 0.4 beats ⋅ min-1 ⋅ mmHg-1). Perindopril prevented the development of hypertension and cardiac hypertrophy and normalized SBRS. BP rose in LH and LL rats after ANG II infusion, but only LH rats, which developed a cardiac hypertrophy, had an impaired SBRS (LH, 1.1 ± 0.2; LN, 2.5 ± 0.2; LL, 2.8 ± 0.3 beats ⋅ min-1 ⋅ mmHg-1). This impairment was partially reversed by an acute ANG II blockade with losartan. These results demonstrate that high BP does not account for the decreased SBRS in LH rats. SBRS impairment could result either from cardiac hypertrophy or from the direct effect of ANG II on the baroreflex loop.This experiment aimed at 1) comparing the spontaneous baroreflex sensitivity (SBRS) in Lyon genetically hypertensive (LH), normotensive (LN), and low blood pressure (LL) rats and 2) assessing some aspects of the mechanisms of its impairment in LH rats. Baroreflex was studied in control animals after an early chronic converting enzyme inhibition with perindopril and after a 4-wk infusion of ANG II in perindopril-treated rats. The SBRS was determined with a previously validated method, using statistical dependence between blood pressure (BP) and heart rate values recorded in freely moving animals. LH rats exhibited high BP, cardiac hypertrophy, and decreased SBRS (LH, 1.3 +/- 0.2; LN, 2.5 +/- 0.4; LL, 2.2 +/- 0.4 beats . min-1 . mmHg-1). Perindopril prevented the development of hypertension and cardiac hypertrophy and normalized SBRS. BP rose in LH and LL rats after ANG II infusion, but only LH rats, which developed a cardiac hypertrophy, had an impaired SBRS (LH, 1.1 +/- 0.2; LN, 2.5 +/- 0.2; LL, 2.8 +/- 0.3 beats . min-1 . mmHg-1). This impairment was partially reversed by an acute ANG II blockade with losartan. These results demonstrate that high BP does not account for the decreased SBRS in LH rats. SBRS impairment could result either from cardiac hypertrophy or from the direct effect of ANG II on the baroreflex loop.


European Journal of Preventive Cardiology | 2012

Is there a BP benefit of changing the time of aspirin administration in treated hypertensive patients

Yves Dimitrov; Jean-Philippe Baguet; Carine Hottelart; Philippe Marboeuf; Jean-Michel Tartière; Michel Ducher; Jean-Pierre Fauvel

Background and design: The effects of aspirin on blood pressure (BP) are controversial and a chronopharmacological effect of aspirin on 24-hour BP was reported recently in otherwise untreated hypertensive patients. The study was designed to test the timing effect of aspirin dosing on 24-hour BP in treated hypertensive patients routinely taking aspirin for cardiovascular prevention. Method and results: Seventy-five patients were randomized into two groups. One group was to receive aspirin in the evening then in the morning for 1 month and the other group in the morning then in the evening, following a cross-over design. The principal assessment criterion was 24-hour systolic BP (SBP) measured by 24-hour ambulatory BP monitoring (ABPM). Patients were aged 65 ± 9 years and had been hypertensive for 12 ± 10 years. They were all taking a mean of 2.8 antihypertensive drugs and did not modify their treatment throughout the study. Of the included subjects, 70% were men and 33% were diabetics. Mean 24-hour SBP values were clinically equivalent and were not statistically different, depending on whether the aspirin was taking in the morning or evening (128.3 ± 1.4 vs. 128.3 ± 1.4 mmHg, respectively). Neither was there any significant difference in diurnal and nocturnal SBP or in 24-hour, diurnal, and nocturnal diastolic BP (DBP). Conclusion: It does not appear useful to advise patients with long-standing hypertension to modify timing of aspirin intake in order to reduce BP values.


Pathologie Biologie | 2002

Efficacité thérapeutique et toxicité des aminosides chez la personne âgée : influence combinée des nouvelles stratégies thérapeutiques et de l'adaptation de posologie

F. Foltz; Michel Ducher; F. Rougier; S. Coudray; Y. Bourhis; M. Druguet; Pascal Maire

This study was aimed to compare with previous results (Grillot et al., 1994), the efficacy of amikacin adaptive optimal control in a geriatric hospital. Patients – During six months, 32 patients (aged of 82 ± 8 years) were included versus 51 during two years (aged of 80 ± 5). The mean age was not different between the two populations (NS, Student test). They received amikacin initial dosage of 17.7 ± 5.1 mg/kg/d (vs 13.3 ± 3.5 for the reference study) and maintenance dosage of 15.1 ± 4.8 mg/kg/d (vs 11.8 ± 5.1 for the reference study). Method – Two efficacy outcomes (E1 and E2) and 1 toxicity outcome (T) were taken into account: E1 estimated the effect of adaptive control on maximal drug level, E2: overall recovery. Toxicity outcome was used: T the nephrotoxicity (increasing creatininemia over 44 μmol/l). Results – All the results are given versus the reference study. 57.6% versus 29.4% of adaptive strategy were once-a-day. E1: Chi square test show that initial dosage and maintenance dosage are greater our study than the previous one (p < 0.05: 78.8% versus 5.9% for initial dosage, 84.4% versus 13.8% for maintenance dosage). E2: 73.6% overall of recovery versus 77% (NS, Chi square test). T: 94% versus 85% (p < 0.05, Chi square test) of creatininemia variation are lower than 44 μmol/l. Duration of treatement is 9.8 ± 4.8 versus 15 ± 9 days (p < 0.5, Student test). Conclusions – Once-a-day strategy in amikacin therapeutic regimen is no more efficient but decreases toxicity and duration treatment.

Collaboration


Dive into the Michel Ducher's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Catherine Cerutti

Centre national de la recherche scientifique

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Christian Paultre

Centre national de la recherche scientifique

View shared research outputs
Top Co-Authors

Avatar

Jean Pierre Fauvel

Centre national de la recherche scientifique

View shared research outputs
Top Co-Authors

Avatar

Roger W. Jelliffe

University of Southern California

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Michel Maurin

Institut national de recherche sur les transports et leur sécurité

View shared research outputs
Researchain Logo
Decentralizing Knowledge