Korean J Clin Pharm.  2016 Jun;26(2):150-162. 10.0000/kjcp.2016.26.2.150.

Comparative Study of First-in-Human Dose Estimation Approaches using Pharmacometrics

• Baek IH

• KMID: 2358067
• DOI: http://doi.org/10.0000/kjcp.2016.26.2.150

Abstract

OBJECTIVE
First-in-human dose estimation is an essential approach for successful clinical trials for drug development. In this study, we systematically compared first-in-human dose and human pharmacokinetic parameter estimation approaches.
METHODS
First-in-human dose estimation approaches divided into similar drug comparison approaches, regulatory guidance based approaches, and pharmacokinetic based approaches. Human clearance, volume of distribution and bioavailability were classified for human pharmacokinetic parameter estimation approaches.
RESULTS
Similar drug comparison approaches is simple and appropriate me-too drug. Regulatory guidance based approaches is recommended from US Food and Drug Administration (FDA) and European Medicines Agency (EMA) regarding no-observed-adverse-effect level (NOAEL) or minimum anticipated biological effect level (MABEL). Pharmacokinetic based approaches are 8 approaches for human clearance estimation, 5 approaches for human volume of distribution, and 4 approaches for human bioavailability.
CONCLUSION
This study introduced and compared all methods for first-in-human dose estimation. It would be useful practically to estimate first-in-human dose for drug development.

Keyword

First-in-human dose; drug development; pharmacometrics; pharmacokinetics; prediction

MeSH Terms

Biological Availability
Humans
No-Observed-Adverse-Effect Level
Pharmacokinetics
United States Food and Drug Administration