ROLE OF LIPOPROTEINS IN THE PLASMA-BINDING OF SDZ PSC-833, A NOVEL MULTIDRUG RESISTANCE-REVERSING CYCLOSPORINE

Citation
N. Simon et al., ROLE OF LIPOPROTEINS IN THE PLASMA-BINDING OF SDZ PSC-833, A NOVEL MULTIDRUG RESISTANCE-REVERSING CYCLOSPORINE, British journal of clinical pharmacology, 45(2), 1998, pp. 173-175
Citations number
10
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
0306-5251
Volume
45
Issue
2
Year of publication
1998
Pages
173 - 175
Database
ISI
SICI code
0306-5251(1998)45:2<173:ROLITP>2.0.ZU;2-T
Abstract
Aims The plasma binding of the cyclosporin D analogue SDZ PSC 833 was investigated in vitro. Methods The plasma total binding constant (corr esponding to the bound-to-free concentration or binding ratio) was det ermined at 37 degrees C by the erythrocyte partitioning technique on p lasma samples from three healthy volunteers and three cancer patients. Lipoproteins were also removed from plasma samples from three healthy volunteers by a standard ultracentrifugal technique. Results SDZ PSC 833 plasma binding was 97.8 +/- 1.1% and 97.3 +/- 0.2% in samples from three healthy volunteers and three cancer patients respectively. Mon than 95% of blood SDZ PSC 833 was distributed in plasma. When the orig inal plasma samples of three individuals were delipidated, SDZ PSC 833 binding was strongly decreased (58% bound to plasma proteins) and whe n lipoproteins were resuspended in the delipidated plasma samples to p roduce varying lipoprotein plasma concentrations, the binding increase d continuously with the fraction of added lipoproteins. When lipoprote ins were resuspended to restore the original lipoprotein plasma conten t, the % plasma-bound SDZ PSC 833 increased to 98.2%, close to the val ue observed with the original plasma (98.7%). Conclusions These result s clearly indicate that SDZ PSC 833 plasma binding is mainly determine d by lipoproteins and that in blood, most of SDZ PSC 833 is distribute d in plasma.