Observations on the pharmacokinetics of low dose aminoglutethimide in patients with advanced breast cancer

Serum aminoglutethimide (AG) and N-acetylaminoglutethimide (NAG) concentrations were measured by high pressure liquid chromatography (HPLC) in 24 postmenopausal women with advanced breast cancer receiving increasing doses of oral AG. Patients received 62.5 mg b.d., 125 mg b.d., 250 mg b.d., and 500 mg b.d. of AG alone, and 500 mg b.d. of AG combined with hydrocortisone (HC) 20 mg b.d. Dose was increased at monthly intervals. Each dose increment was accompanied by a significant rise in serum AG and NAG levels (P less than 0.05). The addition of HC to the dose of 500 mg b.d. of AG did not alter serum AG or NAG concentrations significantly. Although serum AG and NAG levels appeared to increase linearly with dose, serum NAG increased significantly more slowly, leading to a fall in the NAG:AG ratio during therapy. The NAG:AG ratio appeared to stabilise only after about 6 months of treatment.