Relative Performance of Volume of Distribution Prediction Methods for Lipophilic Drugs with Uncertainty in LogP Value.

ABSTRACT:

Purpose

The goal was to assess, for lipophilic drugs, the impact of logP on human volume of distribution at steady-state (VD_ss) predictions, including intermediate fut and Kp values, from six methods: Oie-Tozer, Rodgers-Rowland (tissue-specific Kp and only muscle Kp), GastroPlus, Korzekwa-Nagar, and TCM-New.

Method

A sensitivity analysis with focus on logP was conducted by keeping pKa and fup constant for each of four drugs, while varying logP. VD_ss was also calculated for the specific literature logP values. Error prediction analysis was conducted by analyzing prediction errors by source of logP values, drug, and overall values.

Results

The Rodgers-Rowland methods were highly sensitive to logP values, followed by GastroPlus and Korzekwa-Nagar. T

SUBMITTER: Coutinho AL 

PROVIDER: S-EPMC11196289 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature