Comparative Study of First-in-Human Dose Estimation Approaches using Pharmacometrics.
- Author:
In Hwan BAEK
1
Author Information
1. College of Pharmacy, Kyungsung University, Busan 48434, Republic of Korea. baek@ks.ac.kr
- Publication Type:Comparative Study ; Original Article
- Keywords:
First-in-human dose;
drug development;
pharmacometrics;
pharmacokinetics;
prediction
- MeSH:
Biological Availability;
Humans;
No-Observed-Adverse-Effect Level;
Pharmacokinetics;
United States Food and Drug Administration
- From:Korean Journal of Clinical Pharmacy
2016;26(2):150-162
- CountryRepublic of Korea
- Language:Korean
-
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.
