Serum aminoglutethimide levels: studies of serum half-life, clearance, and patient compliance.

Serum aminoglutethimide was measured in 13 women with mastastatic breast carcinoma who were treated with 1.0 Gm aminoglutethimide and 40 mg hydrocortisone daily over a period of one year. Serum concentrations of aminoglutethimide were used to evaluate drug half-life, clearance, and patient compliance. Mean half-life and clearance rates were determined in six patients. The mean half-life of aminoglutethimide prior to therapy was 13.3 +/- 2.65 (S.D.) hours and fell significantly (P less than 0.01) to 7.3 +/- 2.14 hours after six to 32 weeks of therapy. The mean clearance rate prior to therapy was 2.58 +/- 0.33 (S.D.) 1./hour and increased significantly (P less than 0.01) to 5.29 +/- 1.4 1./hour after therapy. The mean serum concentration was 11.5 +/- 3.6 microgram/ml in seven patients. No significant variation of mean aminoglutethimide concentration from the overall mean was noted during the course of therapy. We conclude that serum aminoglutethimide concentrations are useful in evaluating patient compliance. Our data also suggest that aminoglutethimide increases its own metabolism, which may explain the absence of toxicity symptoms seen late in the treatment period.