title: Inferring systemic exposure from a pharmacokinetic screen: model-free and model-based approaches.
abstract: To infer patterns of average systemic exposure and to estimate individual exposures in phase III clinical trials of a new anxiolytic, two statistical methodologies were applied and compared: non-linear mixed-effect modelling, and a model-free approach based on quartiles of dose-normalized plasma concentrations of the drug. Although the model-based approach provides more quantitative insight about relationships between average exposure and demographic covariates, the model-free approach provides qualitatively similar results about average clearance and quantitatively similar results about individual exposures, and the model-free approach is easy and inexpensive to implement.
authors.affiliation: Department of Clinical Pharmacology, Drug Safety, Sandoz Research Institute, Sandoz Pharmaceuticals Corporation, East Hanover, NJ 07936, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Nedelman
authors.forename: A H
authors.initials: AH
authors.lastname: Karara
authors.forename: C T
authors.initials: CT
authors.lastname: Chang
authors.forename: E
authors.initials: E
authors.lastname: Gibiansky
authors.forename: S
authors.initials: S
authors.lastname: McDonald
authors.forename: W T
authors.initials: WT
authors.lastname: Robinson
mesh_terms: D000328:Adult; D000367:Age Factors; D000704:Analysis of Variance; D014151:Anti-Anxiety Agents / Q000097:blood* / Q000493:pharmacokinetics*; D002243:Carbolines / Q000097:blood / Q000493:pharmacokinetics*; D017321:Clinical Trials, Phase I as Topic / Q000706:statistics & numerical data; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D015233:Models, Statistical; D016011:Normal Distribution; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D018709:Statistics, Nonparametric
chemical_list: D014151:Anti-Anxiety Agents; D002243:Carbolines; C062769:abecarnil