Prediction of human blood-to-plasma drug concentration ratio

Abstract

The objective of this study was to predict Rb (blood/plasma ratio) in humans using a simple method. Human and rat Rb and free fraction in plasma (fp) values were obtained from the literature. The ratio of total red blood cell concentration to the free concentration in plasma (Kb) was calculated using fp and Rb. Four methods were used for the prediction of Rb: (A) use of rat R b; (B) use of Rb calculated from rat Kb and human fp; (C) correlation of human log ((1 -fp)/f p) and human log Kb; and (D) correlation of log D with human log Kb. The Rb of 96 compounds in humans ranged from 0.52 to 2.00, with an average of 0.89. A significant correlation was observed among human log Kb, human log ((1-fp)/fp), and log D; however, no obvious correlation was observed among human Rb, human log ((1-fp)/fp), and log D. The errors within 1.25-fold for methods A-D were 68.3%, 77.6%, 61.5% and 64.8%, respectively. All predictive methods considered here were superior to the use of the average value of human Rb or Rb = 1. Rat Rb corrected by human fp improved the accuracy of the prediction. Method B was the most accurate of the four methods. Copyright © 2010 John Wiley & Sons, Ltd.