Reactive Oxidant Species in Rat Brain Extracellular Fluid

1993 ◽  
pp. 105-131 ◽  
Author(s):  
Matthew E. Layton ◽  
Thomas L. Pazdernik
Keyword(s):  
Rat Brain ◽  
Extracellular Fluid ◽  
Reactive Oxidant Species ◽  
Brain Extracellular Fluid ◽  
Reactive Oxidant

scholarly journals The pH of brain extracellular fluid in the cat

1977 ◽  
Vol 272 (1) ◽  
pp. 137-166 ◽  
Author(s):  
Patricia Cragg ◽  
Lillian Patterson ◽  
M. J. Purves
Keyword(s):  
Extracellular Fluid ◽  
Brain Extracellular Fluid

scholarly journals Kinetics of a nucleoside release from lactide-caprolactone and lactide-glycolide polymers in vitro.

2000 ◽  
Vol 47 (1) ◽  
pp. 59-64
Author(s):  
T Kryczka ◽  
P Grieb ◽  
M Bero ◽  
J Kasperczyk ◽  
P Dobrzynski
Keyword(s):  
Formation Rate ◽  
Local Treatment ◽  
Extracellular Fluid ◽  
Brain Extracellular Fluid ◽  
Artificial Cerebrospinal Fluid ◽  
Fluid Formation ◽  
Further Development ◽  
Kinetics Of ◽  
The Brain

We assessed the rate of release of a model nucleoside (adenosine, 5%, w/w) from nine different lactide-glycolide or lactide-caprolactone polymers. The polymer discs were eluted every second day with an artificial cerebrospinal fluid at the elution rate roughly approximating the brain extracellular fluid formation rate. Adenosine in eluate samples was assayed by HPLC. Three polymers exhibited a relatively constant release of adenosine for over four weeks, resulting in micromolar concentrations of nucleoside in the eluate. This points to the necessity of further development of polymers of this types as intracerebral nucleoside delivery systems for local treatment of brain tumors.

The Development of a PBPK Model for Atomoxetine Using Levels in Plasma, Saliva and Brain Extracellular Fluid in Patients with Normal and Deteriorated Kidney Function

2021 ◽  
Vol 20 ◽  
Author(s):  
Mo'tasem Mohamed Alsmadi ◽  
Laith Naser AL-Eitan ◽  
Nasir Mohammed Idkaidek ◽  
Karem Hasan Alzoubi
Keyword(s):  
Renal Impairment ◽  
Pbpk Model ◽  
Extracellular Fluid ◽  
Cyp2d6 Activity ◽  
Brain Extracellular Fluid ◽  
Hyperactivity Disorder ◽  
Physiologically Based Pharmacokinetic ◽  
Chemically Induced ◽  
Stage Renal Disease ◽  
End Stage

Background: Atomoxetine is a treatment for attention-deficit hyperactivity disorder. It inhibits norepinephrine transporters (NET) in the brain. Renal impairment can reduce hepatic CYP2D6 activity and atomoxetine elimination which may increase its body exposure. Atomoxetine can be secreted in saliva. Objective: The objective of this work was to test the hypothesis that atomoxetine saliva levels (sATX) can be used to predict ATX brain extracellular fluid (bECF) levels and their pharmacological effects in healthy subjects and those with end-stage renal disease (ESRD). Methods: The pharmacokinetics of atomoxetine after intravenous administration to rats with chemically induced acute and chronic renal impairments were investigated. A physiologically-based pharmacokinetic (PBPK) model was built and verified in rats using previously published measured atomoxetine levels in plasma and brain tissue. The rat PBPK model was then scaled to humans and verified using published measured atomoxetine levels in plasma, saliva, and bECF. Results: The rat PBPK model predicted the observed reduced atomoxetine clearance due to renal impairment in rats. The PBPK model predicted atomoxetine exposure in human plasma, sATX, and bECF. Additionally, it predicted that ATX bECF levels needed to inhibit NET are achieved at 80 mg dose. In ESRD patients, the developed PBPK model predicted that the previously reported 65% increase in plasma exposure in these patients could be associated with a 63% increase in bECF. The PBPK simulations showed that there is a significant correlation between sATX and bECF in humans. Conclusion: Saliva levels can be used to predict atomoxetine pharmacological response.

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