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OBJECTIVE Daily adult human exposure to bisphenol A (BPA) has been estimated at <1 µg/kg, with virtually complete first-pass conjugation in the liver in primates but not in mice. We measured unconjugated and conjugated BPA levels in serum from adult female rhesus monkeys and adult female mice after oral administration of BPA and compared findings in mice(More)
Model evaluation is an important issue in population analyses. We aimed to perform a systematic review of all population pharmacokinetic and/or pharmacodynamic analyses published between 2002 and 2004 to survey the current methods used to evaluate models and to assess whether those models were adequately evaluated. We selected 324 articles in MEDLINE using(More)
Pharmacogenetics is now widely investigated and health institutions acknowledge its place in clinical pharmacokinetics. Our objective is to assess through a simulation study, the impact of design on the statistical performances of three different tests used for analysis of pharmacogenetic information with nonlinear mixed effects models: (i) an ANOVA to test(More)
What is already known about this subject? The reviews already published on population PK/PD analyses, focused on theory and presented some clinical applications, evaluated validation practices in limited circumstances, defined interest and sometimes complexity of this approach in drug development or proposed a list of relevant articles. None of them has(More)
Granulocyte colony-stimulating factor (G-CSF) is often used in cancer patients receiving cytotoxic drugs to prevent or reduce high grade neutropenia. We propose a pharmacokinetic/pharmacodynamic model to describe myelotoxicity in both G-CSF treated and non-treated patients that shall increase our understanding of G-CSF effects. The model was built from(More)
Pour-on formulations of endectocides are extensively used to treat and control systemic parasitic diseases in cattle, worldwide. The purpose of the present study was to investigate the influence of the natural licking behaviour of cattle on the plasma and faecal disposition of topically administered ivermectin. Twelve Holstein cattle were given one single(More)
To evaluate by simulation the statistical properties of normalized prediction distribution errors (NPDE), prediction discrepancies (pd), standardized prediction errors (SPE), numerical predictive check (NPC) and decorrelated NPC (NPC(dec)) for the external evaluation of a population pharmacokinetic analysis, and to illustrate the use of NPDE for the(More)
Ivermectin is a worldwide-used antiparasitic drug largely administered to cattle as a topical formulation (pour-on). The actual plasma and faecal disposition of pour-on ivermectin in cattle was documented using an original pharmacokinetic model, and taking into account the oral ingestion of the topical drug following physiological licking as a secondary(More)
The transepithelial intestinal elimination of ivermectin was studied using the intestinal closed-loop model in the rat. The common bile duct was cannulated, and duodenum, jejunum, and ileum were isolated in situ with their intact blood supplies. Following administration of 100, 200, or 400 microg/kg b.wt. ivermectin via the carotid artery, the elimination(More)
The purpose of this study was to develop a whole-body physiologically based pharmacokinetic (WB-PBPK) model for ciprofloxacin for ICU patients, based on only plasma concentration data. In a next step, tissue and organ concentration time profiles in patients were predicted using the developed model. The WB-PBPK model was built using a non-linear mixed(More)