Folinic acid modulation of fluorouracil: tissue kinetics of bolus administration

1989 ◽  
Vol 7 (1) ◽  
Author(s):  
ColinPaul Spears ◽  
BengtG. Gustavsson ◽  
Roland Fr�sing
Keyword(s):  
Folinic Acid ◽  
Bolus Administration ◽  
Kinetics Of ◽  
Tissue Kinetics

Kinetic model for disposition of 6-mercaptopurine in monkey plasma and cerebrospinal fluid

1985 ◽  
Vol 248 (2) ◽  
pp. R147-R156 ◽  
Author(s):  
D. G. Covell ◽  
P. K. Narang ◽  
D. G. Poplack
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Parenchyma ◽  
Lymphocytic Leukemia ◽  
Bolus Administration ◽  
Significant Barrier ◽  
Maintenance Of Remission ◽  
Kinetics Of ◽  
And Diffusion ◽  
Monkey Plasma ◽  
Csf Turnover

The antipurine 6-mercaptopurine (6-MP) is effective in the induction and maintenance of remission in patients with acute lymphocytic leukemia. This report presents a compartmental model that describes the kinetics of 6-MP in the plasma and cerebrospinal fluid (CSF) of the monkey. Analysis is based on simultaneously measured plasma and CSF 6-MP concentrations after intravenous and intraventricular bolus administration. Results indicate that 6-MP administered intraventricularly remains largely in the CSF. Disappearance of 6-MP from CSF is principally due to convective losses at a rate equivalent to CSF turnover. Diffusion of 6-MP across the ependymal surface accounts for only 7% of the 6-MP appearing in the plasma. Conversely the dominant route for entry of 6-MP into the CSF from the plasma is entrainment in choroidally formed CSF. Only 12% of 6-MP in the CSF after intravenous administration can be accounted for by permeation of cerebral capillaries and diffusion through brain parenchyma and across the ependymal surface into CSF. These results indicate that the choroid plexus is not a significant barrier for the transfer of molecules like 6-MP from plasma to CSF.

Size-dependent tissue kinetics of PEG-coated gold nanoparticles

2010 ◽  
Vol 245 (1) ◽  
pp. 116-123 ◽  
Author(s):  
Wan-Seob Cho ◽  
Minjung Cho ◽  
Jinyoung Jeong ◽  
Mina Choi ◽  
Beom Seok Han ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Size Dependent ◽  
Kinetics Of ◽  
Tissue Kinetics

scholarly journals Hippocampal Gene Expression of Deiodinases 2 and 3 and Effects of 3,5-Diiodo-L-Thyronine T2 in Mouse Depression Paradigms

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Natalyia Markova ◽  
Anton Chernopiatko ◽  
Careen A. Schroeter ◽  
Dmitry Malin ◽  
Aslan Kubatiev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Antidepressant Treatment ◽  
Tail Suspension Test ◽  
Separate Experiment ◽  
Bolus Administration ◽  
Hormone Regulation ◽  
Inactive Metabolite ◽  
Kinetics Of

Central thyroid hormone signaling is important in brain function/dysfunction, including affective disorders and depression. In contrast to 3,3′,5-triiodo-L-thyronine (T3), the role of 3,5-diiodo-L-thyronine (T2), which until recently was considered an inactive metabolite of T3, has not been studied in these pathologies. However, both T3 and T2 stimulate mitochondrial respiration, a factor counteracting the pathogenesis of depressive disorder, but the cellular origins in the CNS, mechanisms, and kinetics of the cellular action for these two hormones are distinct and independent of each other. Here, Illumina and RT PCR assays showed that hippocampal gene expression of deiodinases 2 and 3, enzymes involved in thyroid hormone regulation, is increased in resilience to stress-induced depressive syndrome and after antidepressant treatment in mice that might suggest elevated T2 and T3 turnover in these phenotypes. In a separate experiment, bolus administration of T2 at the doses 750 and 1500 mcg/kg but not 250 mcg/kg in naive mice reduced immobility in a two-day tail suspension test in various settings without changing locomotion or anxiety. This demonstrates an antidepressant-like effect of T2 that could be exploited clinically. In a wider context, the current study suggests important central functions of T2, whose biological role only lately is becoming to be elucidated.

Comparative adipose tissue kinetics of thiopental, DDE and 2,4,5,2′,4′,5′-hexachlorobiphenyl in the rat

Xenobiotica ◽  
1985 ◽  
Vol 15 (6) ◽  
pp. 485-491 ◽  
Author(s):  
S. Mühlebach ◽  
P. A. Wyss ◽  
M. H. Bickel
Keyword(s):  
Adipose Tissue ◽  
Kinetics Of ◽  
Tissue Kinetics

scholarly journals Elucidating the kinetics of sodium fluorescein for fluorescence-guided surgery of glioma

2019 ◽  
Vol 131 (3) ◽  
pp. 724-734 ◽  
Author(s):  
Margaret Folaron ◽  
Rendall Strawbridge ◽  
Kimberley S. Samkoe ◽  
Caroline Filan ◽  
David W. Roberts ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Sodium Fluorescein ◽  
Normal Brain ◽  
Normal Brain Tissue ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Kinetics Of ◽  
The Brain ◽  
Pegylated Form ◽  
Tissue Kinetics

OBJECTIVEThe use of the optical contrast agent sodium fluorescein (NaFl) to guide resection of gliomas has been under investigation for decades. Although this imaging strategy assumes the agent remains confined to the vasculature except in regions of blood-brain barrier (BBB) disruption, clinical studies have reported significant NaFl signal in normal brain tissue, limiting tumor-to-normal contrast. A possible explanation arises from earlier studies, which reported that NaFl exists in both pure and protein-bound forms in the blood, the former being small enough to cross the BBB. This study aims to elucidate the kinetic binding behavior of NaFl in circulating blood and its effect on NaFl accumulation in brain tissue and tumor contrast. Additionally, the authors examined the blood and tissue kinetics, as well as tumor uptake, of a pegylated form of fluorescein selected as a potential optical analog of gadolinium-based MRI contrast agents.METHODSCohorts of mice were administered one of the following doses/forms of NaFl: 1) high human equivalent dose (HED) of NaFl, 2) low HED of NaFl, or 3) pegylated form of fluorescein. In each cohort, groups of animals were euthanized 15, 30, 60, and 120 minutes after administration for ex vivo analysis of fluorescein fluorescence. Using gel electrophoresis and fluorescence imaging of blood and brain specimens, the authors quantified the temporal kinetics of bound NaFl, unbound NaFl, and pegylated fluorescein in the blood and normal brain tissue. Finally, they compared tumor-to-normal contrast for NaFl and pegylated-fluorescein in U251 glioma xenografts.RESULTSAdministration of NaFl resulted in the presence of unbound and protein-bound NaFl in the circulation, with unbound NaFl constituting up to 70% of the signal. While protein-bound NaFl was undetectable in brain tissue, unbound NaFl was observed throughout the brain. The observed behavior was time and dose dependent. The pegylated form of fluorescein showed minimal uptake in brain tissue and improved tumor-to-normal contrast by 38%.CONCLUSIONSUnbound NaFl in the blood crosses the BBB, limiting the achievable tumor-to-normal contrast and undermining the inherent advantage of tumor imaging in the brain. Dosing and incubation time should be considered carefully for NaFl-based fluorescence-guided surgery (FGS) of glioma. A pegylated form of fluorescein showed more favorable normal tissue kinetics that translated to higher tumor-to-normal contrast. These results warrant further development of pegylated-fluorescein for FGS of glioma.

scholarly journals Impact of rifampicin-inhibitable transport on the liver distribution and tissue kinetics of erlotinib assessed with PET imaging in rats

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Dorra Amor ◽  
Sébastien Goutal ◽  
Solène Marie ◽  
Fabien Caillé ◽  
Martin Bauer ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Kinetics Of ◽  
Tissue Kinetics
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