Danazol distribution in plasma and cell membranes as related to altered cell properties: Implications for mechanism

Lawrence L. Horstman, Wenche Jy, Manuel Arce, Yeon S. Ahn

Research output: Contribution to journalArticle

10 Scopus citations

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 using a high-pressure liquid chromatography (HPLC) method more reliable than previous radioimmunoassay (RIA) methods. It was found that plasma 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 danazol, concentrations declined to near zero in a similar time frame. RBC concentrations on a packed volume basis were similar to plasma levels. However, the membrane ghosts of RBC contained about 50% of the total RBC 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 in immune disorders may be attributable in part to its intercalation in the lipid bilayer of the plasma membrane, altering antigen/receptor expression to modulate immune reactions. This hypothesis was first suggested when it was observed that the RBC of patients on danazol therapy showed morphological changes and increased resistance to osmotic lysis. It was later shown that danazol in vitro reduces binding of autoantibodies, and protects against complement-mediated lysis, suggesting direct action of danazol on the membranes. This hypothesis is discussed, and danazol's effect in protecting against complement-mediated lysis is described.

Original languageEnglish (US)
Pages (from-to)179-187
Number of pages9
JournalAmerican Journal of Hematology
Volume50
Issue number3
DOIs
StatePublished - Nov 1995

Keywords

  • Complement
  • Gender differences
  • Steroid metabolism

ASJC Scopus subject areas

  • Hematology

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