Development of a 2D-QSAR Model for Tissue-to-Plasma Partition Coefficient Value with High Accuracy Using Machine Learning Method, Minimum Required Experimental Values, and Physicochemical Descriptors.

Journal: European journal of drug metabolism and pharmacokinetics
PMID:

Abstract

BACKGROUND: The demand for physiologically based pharmacokinetic (PBPK) model is increasing currently. New drug application (NDA) of many compounds is submitted with PBPK models for efficient drug development. Tissue-to-plasma partition coefficient (K) is a key parameter for the PBPK model to describe differential equations. However, it is difficult to obtain the K value experimentally because the measurement of drug concentration in the tissue is much harder than that in plasma.

Authors

  • Koichi Handa
    Teijin Institute for Bio-medical Research, Teijin Pharma Limited, 4-3-2 Asahigaoka, Hino-shi, Tokyo 191-8512, Japan.
  • Seishiro Sakamoto
    Pharmaceutical Development Coordination Department, Teijin Pharma Limited, 3-2-1, Kasumigaseki Common Gate West Tower, Kasumigaseki Chiyoda-ku, Tokyo, 100-8585, Japan.
  • Michiharu Kageyama
    Teijin Institute for Bio-medical Research, Teijin Pharma Limited, 4-3-2 Asahigaoka, Hino-shi, Tokyo 191-8512, Japan.
  • Takeshi Iijima
    Toxicology & DMPK Research Department, Teijin Institute for Bio-Medical Research, Teijin Pharma Limited, 4-3-2 Asahigaoka, Hino-shi, Tokyo, 191-8512, Japan.