Open AccessUsing a Vancomycin PBPK Model in Special Populations to Elucidate Case‐Based Clinical PK Observations
Author(s) -
Emoto Chie,
Johnson Trevor N.,
McPhail Brooks T.,
Vinks Alexander A.,
Fukuda Tsuyoshi
Publication year - 2018
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12279
Subject(s) - physiologically based pharmacokinetic modelling , vancomycin , pharmacokinetics , pharmacology , plasma concentration , chemistry , medicine , biology , bacteria , genetics , staphylococcus aureus
Simultaneous changes in several physiological factors may contribute to the large pharmacokinetic (PK) variability of vancomycin. This study was designed to systematically characterize the effects of multiple physiological factors to the altered PK of vancomycin observed in special populations. A vancomycin physiologically based pharmacokinetic (PBPK) model was developed as a PK simulation platform to quantitatively assess the effects of changes in physiologies to the PK profiles. The developed model predicted the concentration‐time profiles in healthy adults and diseased patients. The implementation of developmental changes in both renal and non‐renal elimination pathways to the pediatric model improved the predictability of vancomycin clearance. Simulated PK profiles with a 50% decrease in cardiac output (peak plasma concentration (C max ), 59.9 ng/mL) were similar to those observed in patients before bypass surgery (C max , 55.1 ng/mL). The PBPK modeling of vancomycin demonstrated its potential to provide mechanistic insights into the altered disposition observed in patients who have changes in multiple physiological factors.