Application of microdialysis for study of caffeine distribution into brain and cerebrospinal fluid in rats.
The usefulness of microdialysis was examined for the chronological determination of caffeine concentration in the brain and cerebrospinal fluids (CSF) following intravenous administration of caffeine in rats. The recovery percent of caffeine by microdialysis, the concentration ratio of caffeine in the dialysate against that in the brain tissue or CSF was determined. The recovery percent was proved to be constant at 5 different steady-state plasma concentrations of caffeine (0.1-280 nmol/ml) and in different collecting periods of dialysate ranging from 30 s to 10 min. The mean recovery percent in the brain and CSF were 10.9 and 13.1%, respectively. Thus, microdialysis was proved useful for determination of drug concentration in the tissue and biological fluids with time resolution of more than 30 s. The microdialysis method was then applied for the chronological determination of caffeine concentration in the brain and CSF following intravenous bolus administration. The estimated caffeine concentration in the brain and CSF was the same as those obtained by direct determination in isolated brain and CSF, respectively. Transfer of caffeine from plasma to brain and CSF were further pharmacokinetically analyzed using a modified 2-compartment model. In this kinetic model, the transfer of caffeine between the CSF and brain was neglected, since the mutual transfer of caffeine was not detected in in vivo experiments. Calculated curves were well fitted on observed caffeine concentrations in the plasma, brain and CSF.
Nakazono
T
T
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
Murakami
T
T
Sakai
S
S
Higashi
Y
Y
Yata
N
N
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002110:Caffeine / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D003956:Dialysis; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002110:Caffeine