Prediction of human blood‐to‐plasma drug concentration ratio

Authors:
Publisher website
Google Scholar
Abstract
The objective of this study was to predictRb(blood/plasma ratio) in humans using a simple method. Human and ratRband 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 usingfpandRb. Four methods were used for the prediction ofRb: (A) use of ratRb; (B) use ofRbcalculated from ratKband humanfp; (C) correlation of human log ((1−fp)/fp) and human logKb; and (D) correlation of logDwith human logKb. TheRbof 96 compounds in humans ranged from 0.52 to 2.00, with an average of 0.89. A significant correlation was observed among human logKb, human log ((1−fp)/fp), and logD; however, no obvious correlation was observed among humanRb, human log ((1−fp)/fp), and logD. 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 humanRborRb=1. RatRbcorrected by humanfpimproved the accuracy of the prediction. Method B was the most accurate of the four methods. Copyright © 2010 John Wiley & Sons, Ltd.

This publication has 21 references indexed in Scilit: