Biomedical subjects

Y Merlé

Publications and source records attributed to Y Merlé.

7 recordsLinked to original sources

PubMed1997

Stochastic optimization algorithms of a Bayesian design criterion for Bayesian parameter estimation of nonlinear regression models: application in pharmacokinetics.

This article proposes three stochastic algorithms to optimize a Bayesian design criterion for Bayesian estimation of the parameters of nonlinear regression models; this criterion is the information expected from an experiment. The first algorithm is based on a stochastic version of the simplex with an adaptive sampling procedure. The others are stochastic approximation algorithms: the Kiefer-Wolfowitz and the pseudogradient algorithms. We first present the information criterion and the optimization algorithms. The efficiency of each algorithm for optimizing this Bayesian design criterion is then assessed by a simulation study for a nonlinear model assuming a discrete prior distribution. An application for designing an experiment to estimate the kinetics of radioiodine thyroid uptake is then proposed.

Algorithms↗

PubMed1997

Population pharmacokinetics of clozapine evaluated with the nonparametric maximum likelihood method.

AIMS: To evaluate the distribution of population kinetic parameters for clozapine and their relationship to age and gender in patients on continuous treatment with the drug. METHODS: Retrospective therapeutic drug monitoring data (391 samples from 241 patients) were evaluated using the nonparametric maximum likelihood method. Patients treated concomitantly with drugs known to interact with clozapine were not included. The distribution of clozapine clearance was compared with the distribution of the activity of the drug metabolic enzyme CYP1A2 found in other populations, as recent studies indicate that CYP1A2 is a major determinant for clozapine elimination. The kinetic linearity for clozapine was studied in 41 patients who each provided data from more than one dose level. RESULTS: Clozapine clearance was highly variable in the population and skewed towards high values. Men had higher clearances CL/F (median with 25% and 75% quartiles 38.2 (22.0, 60.0) vs 28.3 (15.2, 48.6) l h(-1)) and a larger volume of distribution V/F (694 (224, 970) vs 401 (189, 932) l) than women. Clearance did not decrease with age in any gender. Clozapine clearance was similarly distributed as the indices of CYP1A2-activity found in other populations by other authors. Evidence of nonlinear kinetics was not found. CONCLUSION: The large kinetic variability for clozapine found in this study implies that the dose of clozapine needs to be individualised over a wide dose range. The similarity of the distribution of clozapine clearance in this study and the CYP1A2-activity in other populations support the assumption that CYP1A2 is a major determinant for clozapine elimination.

Administration, Oral↗

PubMed1995

Bayesian design criteria: computation, comparison, and application to a pharmacokinetic and a pharmacodynamic model.

In this paper 3 criteria to design experiments for Bayesian estimation of the parameters of nonlinear models with respect to their parameters, when a prior distribution is available, are presented: the determinant of the Bayesian information matrix, the determinant of the pre-posterior covariance matrix, and the expected information provided by an experiment. A procedure to simplify the computation of these criteria is proposed in the case of continuous prior distributions and is compared with the criterion obtained from a linearization of the model about the mean of the prior distribution for the parameters. This procedure is applied to two models commonly encountered in the area of pharmacokinetics and pharmacodynamics: the one-compartment open model with bolus intravenous single-dose injection and the Emax model. They both involve two parameters. Additive as well as multiplicative gaussian measurement errors are considered with normal prior distributions. Various combinations of the variances of the prior distribution and of the measurement error are studied. Our attention is restricted to designs with limited numbers of measurements (1 or 2 measurements). This situation often occurs in practice when Bayesian estimation is performed. The optimal Bayesian designs that result vary with the variances of the parameter distribution and with the measurement error. The two-point optimal designs sometimes differ from the D-optimal designs for the mean of the prior distribution and may consist of replicating measurements. For the studied cases, the determinant of the Bayesian information matrix and its linearized form lead to the same optimal designs. In some cases, the pre-posterior covariance matrix can be far from its lower bound, namely, the inverse of the Bayesian information matrix, especially for the Emax model and a multiplicative measurement error. The expected information provided by the experiment and the determinant of the pre-posterior covariance matrix generally lead to the same designs except for the Emax model and the multiplicative measurement error. Results show that these criteria can be easily computed and that they could be incorporated in modules for designing experiments.

Bayes Theorem↗

PubMed1995

Critical influence of resistance to streptogramin B-type antibiotics on activity of RP 59500 (quinupristin-dalfopristin) in experimental endocarditis due to Staphylococcus aureus.

In order to determine the microbiological and pharmacokinetic parameters that best predicted the in vivo antistaphylococcal activity of the streptogramin RP 59500 (quinupristin-dalfopristin), we evaluated the activity in rabbit aortic endocarditis of three regimens of quinupristin-dalfopristin against five strains of Staphylococcus aureus with various streptogramin B-type antibiotic resistance phenotypes and susceptible to streptogramin A-type antibiotics. Quinupristin-dalfopristin was as active as vancomycin against three strains that were susceptible to its streptogramin B component quinupristin, including one strain that was inducibly resistant to erythromycin, but had a significantly decreased activity against two strains that were resistant to quinupristin, for all quinupristin-dalfopristin regimens tested (P < 0.05). The area under the concentration-time curve for quinupristin-dalfopristin in plasma divided by the MIC of quinupristin was the only parameter retained by multilinear regression that predicted the in vivo activity of quinupristin-dalfopristin (P = 0.0001), emphasizing the importance of determining the susceptibility to quinupristin in order to predict the in vivo activity of quinupristin-dalfopristin against S. aureus.

Animals↗

PubMed1994

Designing an optimal experiment for Bayesian estimation: application to the kinetics of iodine thyroid uptake.

We consider the problem of designing an optimal experiment for Bayesian estimation of the parameters of a non-linear model. When their distribution is known, the Bayesian approach allows individual estimation from a small number of measurements; the design determines the accuracy of the estimates. We propose to optimize this design by maximizing a general criterion: the expectation of the information supplied by the experiment. This approach is applied to optimize the two sampling times for Bayesian estimation of the kinetics of radioiodine thyroid uptake from an estimated non-parametric prior distribution.

Bayes Theorem↗

PubMed1994

Population pharmacokinetics of nortriptyline during monotherapy and during concomitant treatment with drugs that inhibit CYP2D6--an evaluation with the nonparametric maximum likelihood method.

Therapeutic drug monitoring data for nortriptyline (674 analyses from 578 patients) were evaluated with the nonparametric maximum likelihood (NPML) method in order to determine the population kinetic parameters of this drug and their relation to age, body weight and duration of treatment. Clearance of nortriptyline during monotherapy exhibited a large interindividual variability and a skewed distribution. A small, separate fraction with a very high clearance, constituting between 0.5% and 2% of the population, was seen in both men and women. This may be explained by the recent discovery of subjects with multiple copies of the gene encoding the cytochrome-P450-enzyme CYP2D6, which catalyses the hydroxylation of nortriptyline. However, erratic compliance with the prescription may also add to this finding. A separate distribution of low clearance values with a frequency corresponding to that of poor metabolizers of CYP2D6 (circa 7% in Caucasian populations) could not be detected. Concomitant therapy with drugs that inhibit CYP2D6 resulted in a major increase in the plasma nortriptyline concentrations. This was caused by a decrease in nortriptyline clearance, whereas the volume of distribution was unchanged. The demographic factors age and body weight had a minor influence on the clearance of nortriptyline which was also unaffected by the duration of treatment.

Administration, Oral↗

PubMed1993

Computer-assisted individual estimation of radioiodine thyroid uptake in Grave's disease.

A computer-assisted Bayesian individual estimation of radioiodine thyroid uptake kinetics for patients suffering from Grave's disease is proposed. The program provides a fast computation of the activity to be administered to a given patient to achieve a target thyroid absorbed dose. This determination relies upon the patient biological covariates and upon a small number of measurements performed during a preliminar kinetic study of radioiodine thyroid uptake. Our results indicate that a two-sample Bayesian approach is reliable when external thyroid counts are performed at 2 h and 168 h after a test dose and has advantages over conventional kinetic experiments in terms of patient acceptability. This method is implemented on widespread computers and interfaced with a patient database. An interactive user interface with in-line data checking is provided. The program could be also a tool to better study the relationship between the absorbed dose and the clinical effect.

Adult↗