1992 Fiscal Year Final Research Report Summary
Study on Drug Distribution into Brain and Cerebrospinal Fluid by Microdialysis
| Project/Area Number |
03671053
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
MURAKAMI Teruo Hiroshima Univ., Associate Sch. of Med. Professor, 医学部, 助教授 (20136055)
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| Project Period (FY) |
1991 – 1992
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| Keywords | Microdialysis / Brain / Cerebrospinal Fluid / Caffeine / Recovery Percent / Brain Distribution / Cerebrospinal Fluids Distribution / Kinetic Analysis |
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| Research Abstract |
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 bilogical 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 as 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 vivo experiments. Calculated curves were well fitted on observed caffeine concentrations in the plasma, brain and CSF.
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