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Role of Altered Drug Metabolism

Richard J. Santen, MD; Allan Lipton, MD; John Kendall, MD

JAMA. 1974;230(12):1661-1665.

Abstract
We used amino-glutethimide and dexamethasone in patients with carcinoma of the breast to abolish adrenal steroidogenesis. Initial studies with this approach, however, did not result in complete adrenal suppression and suggested the possibility of accelerated dexamethasone metabolism. The observation of a twofold reduction in H dexamethasone half-life during amino-glutethimide therapy confirmed this hypothesis. Larger doses of dexamethasone (1.5 to 3.0 mg/day) were administered to 22 patients receiving 1 to 2 gm of amino-glutethimide daily to compensate for rapid dexamethasone metabolism. Complete adrenal suppression for as long as 19 months was then observed, with objective tumor regression in eight subjects and relief of bone pain in three others without producing cushingoid side effects.

(JAMA 230:1661-1665, 1974)

Author Affiliations
From the Department of Internal Medicine (Drs. Santen and Lipton), Division of Endocrinology and Division of Oncology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, Pa, and the Division of Endocrinology (Dr. Kendall), Department of Medicine, University of Oregon Medical School, and the Veterans Administration Hospital, Portland.

Footnotes
Read in part before the American Federation of Clinical Research, Atlantic City, NJ, April 29, 1973.

Reprint requests to Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, PA 17033 (Dr. Santen).

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