An investigation to improve a nonlinear mixed-effects approach for EC50 estimation based on multi-donor dose-response data.

Dose-response relationships are important in assessing the efficacy and potency of compounds, which can usually be characterized by a 4-parameter logistic (4-PL) model estimating EC50, slope factor, lower asymptote, and upper asymptote. EC50, the concentration of a compound that induces a response halfway between the baseline and maximum, is a key quantity to evaluate compound potency. For multi-donor dose-response data, it is often of interest to estimate the overall EC50 (i.

Evaluation of Normalization Methods To Predict CYP3A4 Induction in Six Fully Characterized Cryopreserved Human Hepatocyte Preparations and HepaRG Cells.

Prediction of drug-drug interactions due to cytochrome P450 isoform 3A4 (CYP3A4) overexpression is important because this CYP isoform is involved in the metabolism of about 30% of clinically used drugs from almost all therapeutic categories. Therefore, it is mandatory to attempt to predict the potential of a new compound to induce CYP3A4. Among several in vitro-in vivo extrapolation methods recently proposed in the literature, an approach using a scaling factor, called a d factor, for a given hepatocyte batch to provide extrapolation between in vitro induction data and clinical outcome has been adopted by leading health authorities.

Insulin glargine: a reevaluation of rodent carcinogenicity findings.

The 1995 to 1997 lifetime carcinogenicity studies of insulin glargine in rats and mice were reanalyzed and reassessed for their validity according to current guidelines. In 2-year studies, 50 animals per sex and per group were used. Survival rates between weeks 80 and 90 in female mice and rats were greater than 20 animals in all groups, fulfilling current Food and Drug Administration requirements that enough animals lived long enough to provide adequate exposure to glargine and to be at risk of forming late-developing tumors.

Statistical analysis of regulatory ecotoxicity tests.

ANOVA-type data analysis, i.e..

Self-administered questionnaire compared with interview to assess past-year physical activity.

Purpose: The Modifiable Activity Questionnaire (MAQ) is a physical activity questionnaire shown to be both valid and reliable and was initially designed to be interviewer-administered. After translation and adaptation into French, the objective of the study was to compare past-year physical activity data obtained by self-administration of this questionnaire and by interviewer-administration.

Methods: 84 subjects (22 men, 62 women, age 36-63 yr) enrolled in an ongoing prospective study in France (the SUpplementation en VItamines et Minéraux AntioXydants or SU.