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Influence of aminoglutethimide on plasma levels of medroxyprogesterone acetate
1Department of Clinical Haematology/Oncology, St. James's Hospital, Dublin, Ireland.
Abstract:
To confirm that concomitant administration of aminoglutethimide (AG) reduces plasma levels of medroxyprogesterone acetate (MPA), MPA levels were assayed in six patients with advanced breast cancer receiving the two agents. Patients had disease resistant to AG and were studied during conversion to therapy with MPA. Hydrocortisone was discontinued at the commencement of study and MPA introduced and given at a constant dose of 800 mg daily while AG was reduced in dose from 250 mg b.d. to 125 mg b.d. and then discontinued. MPA levels were measured after two weeks at each dose of AG and after two weeks on MPA alone. Mean MPA levels showed a progressive and significant (P less than 0.01) rise as the AG dose was reduced--180 ng ml-1, 250 ng ml-1 and 740 ng ml-1 respectively. MPA levels were always in excess of the accepted therapeutic level of 100 ng ml-1 and plasma cortisol levels fell in parallel with the rise in MPA levels.
Insights
Aminoglutethimide (AG) reduces medroxyprogesterone acetate (MPA) plasma levels. Reducing AG dosage increased MPA levels, confirming AG
Area of Science:
- Endocrinology
- Pharmacology
- Oncology
Background:
- Medroxyprogesterone acetate (MPA) is used in advanced breast cancer treatment.
- Aminoglutethimide (AG) is an aromatase inhibitor that can affect drug metabolism.
- The interaction between AG and MPA plasma levels requires investigation.
Purpose of the Study:
- To determine if aminoglutethimide (AG) reduces medroxyprogesterone acetate (MPA) plasma levels.
- To quantify the effect of varying AG doses on MPA pharmacokinetics.
Main Methods:
- Six patients with advanced breast cancer resistant to AG were studied.
- Patients received a constant dose of MPA (800 mg daily) while AG dosage was progressively reduced.
- MPA levels were measured at two-week intervals at each AG dose and after AG discontinuation.
Main Results:
- A significant, progressive increase in MPA plasma levels was observed as AG dosage decreased (P < 0.01).
- MPA levels rose from 180 ng/mL to 740 ng/mL as AG was reduced.
- All measured MPA levels remained above the therapeutic threshold of 100 ng/mL.
- Plasma cortisol levels decreased in parallel with increasing MPA levels.
Conclusions:
- Concomitant administration of aminoglutethimide (AG) significantly reduces medroxyprogesterone acetate (MPA) plasma levels.
- Reducing AG dosage leads to a dose-dependent increase in MPA levels.
- This interaction is crucial for optimizing MPA therapy in breast cancer patients.