Linked Life Data

21818805

Source:http://linkedlifedata.com/resource/pubmed/id/21818805

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2011-8-5
pubmed:abstractText
Data on the use of accelerator mass spectrometry (AMS) in conjunction with in vivo studies of macromolecular drugs are scarce. The present study shows the versatility of this technique when investigating the pharmacokinetics (PK) of a macromolecular drug candidate, a polybisphosphonate conjugate (ODX). The aforementioned is a polymer (molecular weight ~30?kDa) constituting a carbohydrate backbone with covalently linked ligands (aldendronate and aminoguanidine) and is intended for treatment of osteoporosis and the therapy of bone metastasis from prostate cancer. The conjugate is prepared through partial oxidation of the carbohydrate and sequential coupling of the ligands by reductive amination. (14)C was incorporated in the conjugate by means of coupling a commercially available (14)C-lysine in the conjugation sequence. Fifteen rats were injected intravenously with (14)C-labelled ODX (150?µg, 14?Bq/rat) and blood samples were collected at 1, 2, 4, 6, and 24?h post-injection (3 rats/time point). Liver, spleen and kidney samples were collected at 4 and 24?h post-injection. Blood from each time point (triplicate) were collected for AMS measurement determining the isotopic ratio ((14)C/(12)C) and consequently the drug concentration in blood. ODX showed a transient presence in blood circulation; 93% of the total dose was cleared from the circulation within 1?h. The half-life after 1?h was estimated to be about 3?h; 0.7% of the administered (14)C dose of ODX remained in circulation after 24?h. The major (14)C accumulation was in the liver, the spleen and the kidneys indicating the probable route of metabolism and excretion. This study demonstrates the versatility of AMS for pharmacological in vivo studies of macromolecules. Labelling with (14)C is relatively simple, inexpensive and the method requires minimal radioactivity, eliminating the need for radioprotection precautions in contrast to methods using scintillation counting.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1097-0231
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 John Wiley & Sons, Ltd.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2453-8
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Application of accelerator mass spectrometry to macromolecules: preclinical pharmacokinetic studies on a polybisphosphonate.
pubmed:affiliation
Ion Physics, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden. mehran.salehpour@angstrom.uu.se
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't