title: Applications of human pharmacokinetic prediction in first-in-human dose estimation.
abstract: Quantitative estimations of first-in-human (FIH) doses are critical for phase I clinical trials in drug development. Human pharmacokinetic (PK) prediction methods have been developed to project the human clearance (CL) and bioavailability with reasonable accuracy, which facilitates estimation of a safe yet efficacious FIH dose. However, the FIH dose estimation is still very challenging and complex. The aim of this article is to review the common approaches for FIH dose estimation with an emphasis on PK-guided estimation. We discuss 5 methods for FIH dose estimation, 17 approaches for the prediction of human CL, 6 methods for the prediction of bioavailability, and 3 tools for the prediction of PK profiles. This review may serve as a practical protocol for PK- or pharmacokinetic/pharmacodynamic-guided estimation of the FIH dose.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, Michigan 48109, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Zou
authors.forename: Yanke
authors.initials: Y
authors.lastname: Yu
authors.forename: Nan
authors.initials: N
authors.lastname: Zheng
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Yang
authors.forename: Hayley J
authors.initials: HJ
authors.lastname: Paholak
authors.forename: Lawrence X
authors.initials: LX
authors.lastname: Yu
authors.forename: Duxin
authors.initials: D
authors.lastname: Sun
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005544:Forecasting; D006801:Humans; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D013045:Species Specificity; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
chemical_list: D004364:Pharmaceutical Preparations