Premium
Application of a hemodialysis clearance prediction model using quantitative structure‐pharmacokinetic relationship analysis
Author(s) -
Suzuki Daisuke,
Aoyama Takahiko,
Nakajima Junki,
Miyamoto Aoi,
Ako Yumina,
Kikkawa Akiyoshi,
Hiraki Kouichi,
Matsumoto Yoshiaki
Publication year - 2020
Publication title -
therapeutic apheresis and dialysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.415
H-Index - 53
eISSN - 1744-9987
pISSN - 1744-9979
DOI - 10.1111/1744-9987.13472
Subject(s) - partition coefficient , pharmacokinetics , hemodialysis , medicine , logarithm , volume of distribution , chromatography , mathematics , chemistry , mathematical analysis
Hemodialysis (HD) is a method used to remove biogenic substances or blood components that cause disease and some drugs used by patients to treat their diseases. Therefore, dosing schedule must be planned according to HD clearance (CL HD ) when medical treatment is provided to patients receiving HD. We aimed to clarify the physical properties (eg, octanol‐water partition coefficient and molecular electronegativity) or pharmacokinetic parameters (eg, volume of distribution) of compounds affecting CL HD and to construct a mathematical model to predict CL HD . The analysis covered individual CL HD data for nine compounds from the literature. The molecular descriptors which are physical properties or pharmacokinetic parameters were calculated using the structural formula of each compound, and searched for factors related to CL HD among the calculated 148 molecular descriptors. Nonlinear mixed‐effects model analysis with CL HD as objective variable and molecular descriptors as explanatory variable was conducted to examine the factor affecting CL HD and develop a model for predicting CL HD . The logarithm of the brain/blood partition coefficient was detected as a factor affecting CL HD . The predictive accuracy of CL HD using the constructed mathematical model with the logarithm of the brain/blood partition coefficient as explanatory variable was adequate.