Application of transcriptome analysis to clinical pharmacology studies.
Clinical pharmacology is the investigation of drug effects in humans. This review discusses the basic tenets of clinical pharmacology research, including pharmacokinetic and pharmacodynamic analysis, therapeutic window, and clinical trial design, and the issues that may arise in the application of transcriptome analysis to clinical pharmacology studies. Examples of how transcriptome analysis can be applied to clinical pharmacology research are described, including a model system of endotoxin challenge (in vitro and in vivo), and an example of a cross-over drug study in normal volunteers. Various data display and analysis methods are also illustrated, including principal component analysis, hierarchical cluster analysis, and pathways analysis.
Hsu
Benjamin
B
Department of Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, Collegeville, PA, USA.
Cass
Lisa
L
Williams
William V
WV
D000818:Animals; D002986:Clinical Trials as Topic; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004731:Endotoxins / Q000378:metabolism; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010601:Pharmacology, Clinical; D011506:Proteins / Q000032:analysis*; D014158:Transcription, Genetic
D004731:Endotoxins; D011506:Proteins