Linked Life Data

8850317

Source:http://linkedlifedata.com/resource/pubmed/id/8850317

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1996-12-10
pubmed:abstractText
The effects of i.v. formulations on the pharmacokinetics were examined for two antitumor agents with different lipophilicities: rhizoxin and palmitoyl-rhizoxin (RS-1541). Blood disposition and tissue distributions in rats were evaluated using three formulations: polyethylene glycol 400 (PEG)/dimethylacetamide (DMA) solution, colloidal solution, and lipid emulsions composed of dioctanoyl decanoyl glycerol (ODO) and polyoxyethylene-(60)-hydrogenated castor oil (HCO-60). The effects of emulsion particle size on the pharmacokinetics were also investigated. Rhizoxin rapidly disappeared from the plasma and showed high distribution in the tissues, and in vitro rapidly degraded in the plasma independent of the formulations used. In in vitro plasma, rhizoxin was easily released from the emulsion particles. In contrast to rhizoxin, the pharmacokinetics of RS-1541 with greater lipophilicity changed considerably depending on the formulations. The emulsions showed high and sustained plasma concentrations for RS-1541. RS-1541 was stably incorporated in the emulsion droplets and protected from the degradation when it was applied as an emulsion. Tissue distributions of RS-1541 in rats after an injection as lipid emulsion were strongly affected by the emulsion particle size. Small size emulsions (100-110 nm) showed the highest plasma concentrations of RS-1541, though they were unable to suppress distributions of the drug in peripheral tissues. Emulsions larger than 200 nm (approx.) in size, on the contrary, effectively inhibited the drug from entering the bone marrow, small intestine and other non-reticuloendothelial system (non-RES) organs, where many cytotoxic compounds showed undesired toxicities. These results indicate that the lipid emulsions composed of ODO and HCO-60 could be a promising and effective DDS carrier for RS-1541, which is highly lipophilic and stabilized in the emulsions. This was not the case for rhizoxin, however, which was less lipophilic than palmitoyl analogue RS-1541. The work described herein has demonstrated that by properly selecting the particle size, these lipid emulsions can control the behavior of a drug in the body.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0918-6158
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
252-8
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Pharmacokinetics of highly lipophilic antitumor agent palmitoyl rhizoxin incorporated in lipid emulsions in rats.
pubmed:affiliation
Analytical and Metabolic Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
pubmed:publicationType
Journal Article