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Sainte-Foy-lès-Lyon, France

Goutell S.,Service Pharmaceutique Groupement Hospitalier Of Geriatrie | Goutell S.,University Claude Bernard Lyon 1 | Goutell S.,CNRS Biometry and Evolutionary Biology Laboratory | Baudry T.,Service de Maladies Infectieuses et Tropicales | And 14 more authors.
Antimicrobial Agents and Chemotherapy

Limited data on the pharmacokinetics and pharmacodynamics (PK/PD) of unboosted atazanavir (uATV) in treatment-experienced patients are available. The aim of this work was to study the PK/PD of unboosted atazanavir in a cohort of HIV-infected patients. Data were available for 58 HIV-infected patients (69 uATV-based regimens). Atazanavir concentrations were analyzed by using a population approach, and the relationship between atazanavir PK and clinical outcome was examined using logistic regression. The final PK model was a linear one-compartment model with a mixture absorption model to account for two subgroups of absorbers. The mean (interindividual variability) of population PK parameters were as follows: clearance, 13.4 liters/h (40.7%), volume of distribution, 71.1 liters (29.7%), and fraction of regular absorbers, 0.49. Seven subjects experienced virological failure after switch to uATV. All of them were identified as low absorbers in the PK modeling. The absorption rate constant (0.38 ± 0.20 versus 0.75 ± 0.28 h-1; P = 0.002) and ATV exposure (area under the concentration-time curve from 0 to 24 h [AUC0-24], 10.3 ± 2.1 versus 22.4 ± 11.2mg·h·liter-1; P = 0.001) were significantly lower in patients with virological failure than in patients without failure. In the logistic regression analysis, both the absorption rate constant and ATV trough concentration significantly influenced the probability of virological failure. A significant relationship between ATV pharmacokinetics and virological response was observed in a cohort of HIV patients who were administered unboosted atazanavir. This study also suggests that twice-daily administration of uATV may optimize drug therapy. Copyright © 2013, American Society for Microbiology. All Rights Reserved. Source

Recurrent ideological discourses on hospital are significative of what is expected from it and even further than its therapeutical fonction: its very symbolic fonctions for society. Nominative registered delivery of drugs in the care units by pharmaceutical assistants is a specific organisation of hospital work. The aim of this paper is to assess within a sociological perspective the consequences of this organization on the pharmaceutical assistants and on the hospital more broadly. Based on a qualitative inquiry, this work is constructed on semi-structured interviews and daily observations registered during our six-months presence in the units. One first result is that this organization of the pharmaceutical work helps the pharmaceutical assistants to integrate in the hospital and strengthens their focus on the work. Another result, less expected, is the way this work helped spread new discourses about hospital ressources management. In the end, this work points out the interest of a "bottum-up" changing practice model compared to the regular "top down" mangement. © 2011 Elsevier Masson SAS. All rights reserved. Source

Salmon D.,Service Pharmaceutique
International journal of pharmaceutics

Hypospadias is a birth defect in which the urinary tract opening is not at the tip of the penis. Hypospadias surgery is frequently complicated by healing deficiencies. Topical treatments with oestrogens were reported to improve healing. In the present study, ex vivo percutaneous absorption of promestriene, a synthetic oestrogen resulting of the double esterification of estradiol was conducted as a pre-requisite for further clinical trial in infants. Penetration of promestriene into infant foreskin treated with commercial oil in water emulsion (10 μg mg(-1)) for 24 h was characterized showing controlled release properties enabling epidermal concentration more than six times higher than dermal concentration (4.13±2.46 mg g(-1) versus 0.62±0.84 mg g(-1), respectively). Furthermore, apparent promestriene fluxes into and through the skin (i.e., 1.5 μg cm(-2) h(-1) and<0.89 μg cm(-2) h(-1), respectively) were calculated from (i) drug amount retained into epidermis and dermis, or (ii) the limit of detection into the receptor fluid. In conclusion, less than 2% of initial dose were absorbed within 24h which compared well with others steroids applied topically in colloidal systems. Copyright © 2013. Published by Elsevier B.V. Source

Modeling of CD4 cells counts response was performed through a Non-Hierarchical-descendant process with profoundly immunocompromised symptomatic patients under nevirapine or efavirenz-based antiretroviral regimen in Abidjan. Similar CD4 cells count trajectories have been modelled in meta-trajectories linked to patients' classes. Global immunological response is similar between "nevirapine group" and "efavirenz group" but the model showed an internal variation of this response in each group. In the both groups, some variables presented a significant variation between classes: average CD4, CD4 Nadir, CD4 peak and average gain of CD4. In "nevirapine group", these following parameters vary significantly between classes: mean weight, mean haemoglobin count and mean increase in haemoglobin count and sex. It's also important to note that, all meta-trajectories began with distinctive categories of baseline CD4 cells counts. Other explanatory factors must be sought because the characteristics we have chosen to describe patients'classes, are not exhaustive. © 2011 Société Française de Pharmacologie et de Thérapeutique. Source

Gabriel L.,Service Pharmaceutique | Tod M.,University of Lyon | Goutelle S.,Service Pharmaceutique | Goutelle S.,University of Lyon | Goutelle S.,CNRS Biometry and Evolutionary Biology Laboratory
Clinical Pharmacokinetics

Background: A simple method to predict drug–drug interactions mediated by cytochrome P450 enzymes (CYPs) on the basis of in vivo data has been previously applied for several CYP isoforms but not for CYP1A2. The objective of this study was to extend this method to drug interactions caused by CYP1A2 inhibitors and inducers. Methods: First, initial estimates of the model parameters were obtained using data from the literature. Then, an external validation of these initial estimates was performed by comparing model-based predicted area under the concentration–time curve (AUC) ratios with observations not used in the initial estimation. Third, refined estimates of the model parameters were obtained by Bayesian orthogonal regression using Winbugs software, and predicted AUC ratios were compared with all available observations. Finally, predicted AUC ratios for all possible substrates–inhibitors and substrates–inducers were computed. Results: A total of 100 AUC ratios were retrieved from the literature. Model parameters were estimated for 19 CYP1A2 substrate drugs, 26 inhibitors and seven inducers, including tobacco smoking. In the external validation, the mean prediction error of the AUC ratios was −0.22, while the mean absolute error was 0.97 (37 %). After the Bayesian estimation step, the mean prediction error was 0.11, while the mean absolute error was 0.43 (22 %). The AUC ratios for 625 possible interactions were computed. Conclusion: This analysis provides insights into the interaction profiles of drugs poorly studied so far and can help to identify and manage significant interactions in clinical practice. Those results are now available to the community via a web tool (http://www.ddi-predictor.org). © 2016 Springer International Publishing Switzerland Source

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