DANAZOL DISTRIBUTION IN PLASMA AND CELL-MEMBRANES AS RELATED TO ALTERED CELL PROPERTIES - IMPLICATIONS FOR MECHANISM

Citation
Ll. Horstman et al., DANAZOL DISTRIBUTION IN PLASMA AND CELL-MEMBRANES AS RELATED TO ALTERED CELL PROPERTIES - IMPLICATIONS FOR MECHANISM, American journal of hematology, 50(3), 1995, pp. 179-187
Citations number
58
Categorie Soggetti
Hematology
ISSN journal
03618609
Volume
50
Issue
3
Year of publication
1995
Pages
179 - 187
Database
ISI
SICI code
0361-8609(1995)50:3<179:DDIPAC>2.0.ZU;2-C
Abstract
Concentrations of danazol in patient plasma and red blood cells (RBC) were assayed over a 6-month period in 75 patients on danazol therapy u sing a high-pressure liquid chromatography (HPLC) method more reliable than previous radioimmunoassay (RIA) methods, It was found that plasm a danazol rose regularly for 15 days after the beginning of treatment, reaching a steady state plateau of 175 +/- 76 ng/ml in 20 patients on normal dose, and less for lower dose schedules. After stopping danazo l, concentrations declined to near zero in a similar time frame. RBC c oncentrations on a packed volume basis were similar to plasma levels. However, the membrane ghosts of RBC contained about 50% of the total R BC danazol, implying about 100-fold higher concentration in membranes than in plasma, Similar distributions were obtained in vitro with both RBC and platelets, and were confirmed by 14-C-labeled danazol, These findings tend to support the hypothesis that the benefits of danazol i n immune disorders may be attributable in part to its intercalation in the lipid bilayer of the plasma membrane, altering antigen/receptor e xpression to modulate immune reactions. This hypothesis was first sugg ested when it was observed that the RBC of patients on danazol therapy showed morphological changes and increased resistance to osmotic lysi s. It was later shown that danazol in vitro reduces binding of autoant ibodies, and protects against complement-mediated lysis, suggesting di rect action of danazol on the membranes, This hypothesis is discussed, and danazol's effect in protecting against complement-mediated lysis is described. (C) 1995 Wiley-Liss, Inc.