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Population Pharmacokinetic Method to Predict Within-Subject Variability Using Single-Period Clinical Data

Authors :
Won-ho Kang
Jae-yeon Lee
Jung-woo Chae
Kyeong-Ryoon Lee
In-hwan Baek
Min-Soo Kim
Hyun-moon Back
Sangkeun Jung
Craig Shaffer
Rada Savic
Hwi-yeol Yun
Source :
Pharmaceuticals, Vol 14, Iss 2, p 114 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

Sample sizes for single-period clinical trials, including pharmacokinetic studies, are statistically determined by within-subject variability (WSV). However, it is difficult to determine WSV without replicate-designed clinical trial data, and statisticians typically estimate optimal sample sizes using total variability, not WSV. We have developed an efficient population-based method to predict WSV accurately with single-period clinical trial data and demonstrate method performance with eperisone. We simulated 1000 virtual pharmacokinetic clinical trial datasets based on single-period and dense sampling studies, with various study sizes and levels of WSV and interindividual variabilities (IIVs). The estimated residual variability (RV) resulting from population pharmacokinetic methods were compared with WSV values. In addition, 3 × 3 bioequivalence results of eperisone were used to evaluate method performance with a real clinical dataset. With WSV of 40% or less, regardless of IIV magnitude, RV was well approximated by WSV for sample sizes greater than 18 subjects. RV was underestimated at WSV of 50% or greater, even with datasets having low IIV and numerous subjects. Using the eperisone dataset, RV was 44% to 48%, close to the true value of 50%. In conclusion, the estimated RV accurately predicted WSV in single-period studies, validating this method for sample size estimation in clinical trials.

Details

Language :
English
ISSN :
14020114 and 14248247
Volume :
14
Issue :
2
Database :
Directory of Open Access Journals
Journal :
Pharmaceuticals
Publication Type :
Academic Journal
Accession number :
edsdoj.8616252597634ab59a550a02c6d48520
Document Type :
article
Full Text :
https://doi.org/10.3390/ph14020114