TY - JOUR
T1 - An Application of Microdialysis to Drug Tissue Distribution Study
T2 - In Vivo Evidence for Free-Ligand Hypothesis and Tissue Binding of /3-Lactam Antibiotics in Interstitial Fluids
AU - Deguchi, Yoshiharu
AU - Terasaki, Tetsuya
AU - Yamada, Hiroko
AU - Tsuji, Akira
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1992
Y1 - 1992
N2 - am antibiotics, the microdialysis technique has been employed for the lung, the muscle and the liver in rats. Cefminox, a cephem antibiotic, and SY5555, a new penem antibiotic, were used in the present study. During the constant infusion of each antibiotic with simultaneous infusion of antipyrine, the microdialysis studies were performed and the dialysate concentrations were determined. The dialysate concentration was extrapolated to the in vivo unbound concentration in tissue interstitial fluids (Cisf u) according to the extrapolation method which was derived from the clearance concept. This extrapolation method incorporates the effective dialysis coefficient of a reference compound, antipyrine, which is used to correct the difference between in vivo and in vitro permeabilities of microdialysis fiber. The values of Cisf u values for cefminox and SY5555 in the lung, muscle and liver were close to the unbound concentrations in the venous plasma leaving these organs. Furthermore, good coincidences were obtained between the unbound concentrations of SY5555 in lung and muscle interstitial fluids estimated from the total concentrations in homogenized tissues and those extrapolated by the microdialysis studies. Consequently, the present microdialysis studies provided the in vivo evidence that 1) the free-ligand hypothesis for extravascular equilibration of β-lactam antibiotics is true, and that 2) β-lactam antibiotics are restricted in the interstitial space in a noneliminating organ and bind only with albumin existing in this space.
AB - am antibiotics, the microdialysis technique has been employed for the lung, the muscle and the liver in rats. Cefminox, a cephem antibiotic, and SY5555, a new penem antibiotic, were used in the present study. During the constant infusion of each antibiotic with simultaneous infusion of antipyrine, the microdialysis studies were performed and the dialysate concentrations were determined. The dialysate concentration was extrapolated to the in vivo unbound concentration in tissue interstitial fluids (Cisf u) according to the extrapolation method which was derived from the clearance concept. This extrapolation method incorporates the effective dialysis coefficient of a reference compound, antipyrine, which is used to correct the difference between in vivo and in vitro permeabilities of microdialysis fiber. The values of Cisf u values for cefminox and SY5555 in the lung, muscle and liver were close to the unbound concentrations in the venous plasma leaving these organs. Furthermore, good coincidences were obtained between the unbound concentrations of SY5555 in lung and muscle interstitial fluids estimated from the total concentrations in homogenized tissues and those extrapolated by the microdialysis studies. Consequently, the present microdialysis studies provided the in vivo evidence that 1) the free-ligand hypothesis for extravascular equilibration of β-lactam antibiotics is true, and that 2) β-lactam antibiotics are restricted in the interstitial space in a noneliminating organ and bind only with albumin existing in this space.
KW - Antipyrine
KW - dialysis clearance
KW - extracellular model
KW - interstitial fluid
KW - liver
KW - lung
KW - microdialysis
KW - muscle
KW - physiological pharmacokinetics
KW - β-lactam antibiotics
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U2 - 10.1248/bpb1978.15.79
DO - 10.1248/bpb1978.15.79
M3 - Article
C2 - 1403606
AN - SCOPUS:0026587967
VL - 15
SP - 79
EP - 89
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
SN - 0918-6158
IS - 2
ER -