Document Detail


Biodistribution and pharmacokinetics of PEG-10kDa-cholecystokinin-10 in rats after different routes of administration.
MedLine Citation:
PMID:  20158487     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cholecystokinin, produced in the proximal small intestine, is a short acting satiating peptide hormone. CCK-10, before and after mono-iodination, was previously coupled to 10kDa polyethylene glycol (PEG). The formed conjugates PEG10kDa-CCK-10 and PEG10kDa-[(127)I]-CCK-10 show after i.p. administration to rats a sustained food intake reduction during 8h in comparison to 2h for free CCK-10. The present study examined the blood pharmacokinetics of this pharmacological interesting molecule by means of PEG10kDa-[(123)I]-CCK-10 following intravenous, intraperitoneal, intramuscular and nasal administration and the biodistribution after i.p. administration. HPLC analysis with radiometric detection allowed the differentiation between inorganic iodide and the intact tracer in blood. Blood kinetics after i.v. injection was fitted to a bi-exponential with a distribution half-life of 15 min and with an elimination half-life of 8 hours for intact PEG10kDa-[(123)I]-CCK-10. The biodistribution studies showed a higher accumulation of the tracer for all administration routes in organs expressing CCK receptors localized in the gastrointestinal tract such as pancreas, duodenum and small intestine. No indication of blood brain barrier crossing for the conjugate could be observed independently of the administration route. Main clearance was via the urinary pathway.
Authors:
Fabián León-Tamariz; Isabelle Verbaeys; Maurits Van Boven; Marcel De Cuyper; Johan Buyse; Peter de Witte; Alfons Verbruggen; Marnix Cokelaere
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Current drug delivery     Volume:  7     ISSN:  1875-5704     ISO Abbreviation:  Curr Drug Deliv     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-20     Completed Date:  2010-07-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101208455     Medline TA:  Curr Drug Deliv     Country:  United Arab Emirates    
Other Details:
Languages:  eng     Pagination:  137-43     Citation Subset:  IM    
Affiliation:
Laboratory of Toxicology and Bromatology, Faculty of Pharmaceutical Sciences; Katholieke Universiteit Leuven, Leuven, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cholecystokinin / administration & dosage,  blood*,  urine
Drug Administration Routes
Drug Carriers / administration & dosage,  chemical synthesis,  chemistry,  pharmacokinetics*
Half-Life
Iodine Radioisotopes / blood*,  urine
Male
Peptide Fragments / administration & dosage,  blood*,  urine
Polyethylene Glycols / administration & dosage,  chemistry,  pharmacokinetics*
Rats
Rats, Wistar
Tissue Distribution
Chemical
Reg. No./Substance:
0/Drug Carriers; 0/Iodine Radioisotopes; 0/Peptide Fragments; 0/Polyethylene Glycols; 25842-57-3/cholecystokinin 10 C-terminal fragment; 9011-97-6/Cholecystokinin

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