Aminoglutethimide therapy in breast cancer: relationship of blood levels to drug-related side effects.
Aminoglutethimide (AG) is now an established agent for producing a 'medical adrenalectomy' in patients with breast cancer. A number of annoying symptoms can occur in some patients placed on this medication. It has been suggested that the expression of symptoms may be related to the ability of the patient to acetylate AG to N-acetyl aminoglutethimide (NAG). Using high-pressure liquid chromatography (HPLC), we examined blood levels of AG and NAG in patients with breast cancer and compared the levels to the expression and frequency of drug symptoms. 43% of patients examined were judged to be slow acetylators in that 92% of the drug remained unacetylated irrespective of the dose administered. There was no significant correlation between acetylator status (rapid vs. slow) and the frequency of drug symptoms noted. In contrast, there was a significant correlation between the level of AG itself and the frequency of symptoms. 80% of patients with blood levels exceeding 12 mg/l had drug-related symptoms while only 36% of patients with levels below 8 mg/l showed symptoms (chi 2 p less than 0.05). 67% of patients with NAG levels in excess of 4 mg/l had symptoms. These findings indicate the presence of slow and rapid acetylators of AG in a breast cancer population and the importance of determining blood levels of the drug to minimize the onset of drug-related symptoms in some patients without losing drug efficacy.
D000616:Aminoglutethimide / Q000009:adverse effects* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D014581:Urticaria / Q000139:chemically induced
D000616:Aminoglutethimide