Prediction of human blood‐to‐plasma drug concentration ratio

The objective of this study was to predict R(b) (blood/plasma ratio) in humans using a simple method. Human and rat R(b) and free fraction in plasma (f(p)) values were obtained from the literature. The ratio of total red blood cell concentration to the free concentration in plasma (K(b)) was calculated using f(p) and R(b). Four methods were used for the prediction of R(b): (A) use of rat R(b); (B) use of R(b) calculated from rat K(b) and human f(p); (C) correlation of human log ((1-f(p))/f(p)) and human log K(b); and (D) correlation of log D with human log K(b). The R(b) 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 K(b), human log ((1-f(p))/f(p)), and log D; however, no obvious correlation was observed among human R(b), human log ((1-f(p))/f(p)), 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 R(b) or R(b)=1. Rat R(b) corrected by human f(p) improved the accuracy of the prediction. Method B was the most accurate of the four methods.