Clinical Pharmacokinetics

, Volume 13, Issue 6, pp 393–406 | Cite as

Alterations in the Metabolism of Oestrogens During Treatment with Aminoglutethimide in Breast Cancer Patients

Preliminary Findings
  • P. E. Lønning
  • S. Kvinnsland
  • T. Thorsen
  • P. M. Ueland
Original Research Article

Summary

In this small study, the effect of aminoglutethimide on the disposition of oestrogens in women with advanced breast cancer was investigated using bolus injections of 4-[14C]-oestradiol and 6,7-[3H]-oestrone sulphate, alone or in combination.

No alterations in oestrogen disposition were seen after short term (6 hours) aminoglutethimide administration. During long term (3 weeks to 8 months) aminoglutethimide treatment mean 4-[14C]-oestradiol clearance was not changed. 14C-Oestrone sulphate AUC was reduced by 43% at a low dose of aminoglutethimide (125mg twice daily) and by 65% at a high dose (250mg 4 times daily) with hydrocortisone acetate 25mg twice daily. The oestrone sulphate terminal elimination rate constant (λz) was concurrently increased (mean of 46 and 79%, respectively, with the 2 dosage regimens).

A possible increase in oestrone sulphate clearance during long term treatment was tested for by injecting 6,7-[3H]-oestrone sulphate. These studies revealed a marked increase (mean 104%) in oestrone sulphate clearance in patients receiving the high dose aminoglutethimide schedule.

Following injection of 4-[14C]-oestradiol plus 6,7-[3H]-oestrone sulphate, the fraction of 4-[14C]-oestradiol metabolised to oestrone sulphate was found to be reduced in all patients (mean 13%). A mean increase of 80% in the urinary excretion of 14C-oestriol was observed after 4-[14C]-oestradiol administration.

Our results, although preliminary, suggest that aminoglutethimide is a potent inducer of aminoglutethimide metabolism, thereby producing a significant reduction in plasma bioavailability of oestrone sulphate. These effects may have a role in the action of aminoglutethimide, a finding which warrants further investigation.

Keywords

Advanced Breast Cancer Clinical Endocrinology Oestriol Santen Aminoglutethimide 

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Copyright information

© ADIS Press Limited 1987

Authors and Affiliations

  • P. E. Lønning
    • 1
  • S. Kvinnsland
    • 1
  • T. Thorsen
    • 1
  • P. M. Ueland
    • 1
  1. 1.Departments of Biochemical Endocrinology, Oncology and Clinical Pharmacology Unit, Department of PharmacologyUniversity of BergenBergenNorway

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