Document Detail


Infusion rates and drug distribution in brain tumor models in rats.
MedLine Citation:
PMID:  16206734     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECT: The aim of this study was to investigate the optimal delivery rates of chemotherapy for the treatment of central nervous system tumors and to determine whether local delivery can lower toxicity profiles and increase target concentrations of chemotherapy. METHODS: The authors used two brain tumor models in rats. Slow (1 microl/hour) and fast (10 microl/hour) pumps were used to deliver chemotherapy--carboplatin, doxorubicin, and a high-molecular-weight transferrin-doxorubicin conjugate to the brains of normal rats and rats previously injected with F98 or 9L rat brain tumor cells. Brains were cut in 1-mm sections rostral and caudal from the infusion point. Slices were analyzed for doxorubicin and platinum by fluorescence and atomic absorption, respectively. In the normal tissues, the volume of drug distribution is generally greater at the faster flow rate. In abnormal tissues, distribution is similar at slow and fast infusion rates for low-molecular-weight drugs and greater at slow rates for a high-molecular-weight targeted toxin. CONCLUSIONS: After local administration the distribution of chemotherapy appears to be significantly influenced by tumor metabolism. Additional studies are needed to determine the optimal delivery rates for the interaction of the drug with the targeted tumor.
Authors:
Andleeb Khan; George I Jallo; Ya J Liu; Benjamin S Carson; Michael Guarnieri
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurosurgery     Volume:  102     ISSN:  0022-3085     ISO Abbreviation:  J. Neurosurg.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2005-10-06     Completed Date:  2005-10-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0253357     Medline TA:  J Neurosurg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  53-8     Citation Subset:  AIM; IM    
Affiliation:
Division of Pediatric Neurosurgery, The Johns Hopkins Hospital, Baltimore, Maryland 21287-8811, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibiotics, Antineoplastic / administration & dosage*,  pharmacokinetics*
Antineoplastic Agents / administration & dosage*,  pharmacokinetics*
Blood-Brain Barrier
Brain Neoplasms / drug therapy*,  veterinary
Carboplatin / administration & dosage*,  pharmacokinetics*
Disease Models, Animal
Doxorubicin / administration & dosage*,  pharmacokinetics*
Female
Infusion Pumps
Molecular Weight
Rats
Rats, Inbred F344
Transferrin / administration & dosage,  pharmacokinetics
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Antineoplastic Agents; 11096-37-0/Transferrin; 23214-92-8/Doxorubicin; 41575-94-4/Carboplatin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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