Abstract
The urinary excretion during 24 h of aminoglutethimide (AG) its major metabolite (N-acetylAG) and two minor metabolites (N-formylAG and nitroG) were measured in 10 volunteers given AG who had been typed for acetylator phenotype using sulphadimidine. The slow acetylators of sulphadimidine excreted more AG (mean 28% of the administered dose) than did the fast acetylators (12%), but the latter excreted more of the dose as N-acetylAG (8.8%) than did the former (3.9%). NitroG and N-formylAG were minor urinary metabolites of AG in humans. The former was more abundant in the urine of slow acetylators (0.10% of the dose) than in that of fast acetylators (0.047%), whereas the respective proportions of doses excreted as the N-formyl derivative (0.475 and 0.465%) were not significantly different for the two acetylator phenotypes. These results show that AG is among those drugs that are polymorphically acetylated in humans.
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- Aboul-Enein H. Y., Schauberger C. W., Hansen A. R., Fischer L. J. Synthesis of an active hydroxylated glutethimide metabolite and some related analogs with sedative-hypnotic and anticonvulsant properties. J Med Chem. 1975 Jul;18(7):736–741. doi: 10.1021/jm00241a019. [DOI] [PubMed] [Google Scholar]
- Douglas J. S., Nicholls P. J. The partial fate of aminoglutethimide in man. J Pharm Pharmacol. 1972 Dec;24(Suppl):150P–150P. [PubMed] [Google Scholar]
- EVANS D. A., WHITE T. A. HUMAN ACETYLATION POLYMORPHISM. J Lab Clin Med. 1964 Mar;63:394–403. [PubMed] [Google Scholar]
- Evans D. A. An improved and simplified method of detecting the acetylator phenotype. J Med Genet. 1969 Dec;6(4):405–407. doi: 10.1136/jmg.6.4.405. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perry H. M., Jr, Tan E. M., Carmody S., Sakamoto A. Relationship of acetyl transferase activity to antinuclear antibodies and toxic symptoms in hypertensive patients treated with hydralazine. J Lab Clin Med. 1970 Jul;76(1):114–125. [PubMed] [Google Scholar]
- Santti R. S., Hopsu-Havu V. K. Transformylation of carcinogenic aromatic by kynerenine formamidase: a detoxication mechanism. Biochem Pharmacol. 1968 Jun;17(6):1110–1113. doi: 10.1016/0006-2952(68)90370-5. [DOI] [PubMed] [Google Scholar]
- Smith I. E., Fitzharris B. M., McKinna J. A., Fahmy D. R., Nash A. G., Neville A. M., Gazet J. C., Ford H. T., Powles T. J. Aminoglutethimide in treatment of metastatic breast carcinoma. Lancet. 1978 Sep 23;2(8091):646–649. doi: 10.1016/s0140-6736(78)92759-9. [DOI] [PubMed] [Google Scholar]
- Stillwell W. G., Lindberg C., Hartvig P. Artifacts formed in the metabolic study of pethidine. Acta Pharm Suec. 1978;15(1):71–75. [PubMed] [Google Scholar]
- Tabarelli S., Uehleke H. N-hydroxylation of 4,4'-diaminodiphenylsulphone in liver microsomes and in vivo. Xenobiotica. 1971 Jul-Oct;1(4):501–502. doi: 10.3109/00498257109041517. [DOI] [PubMed] [Google Scholar]
- Tyler T. R., Buhs R. P., VandenHuevel W. J. Identification of the mononitro derivative of dapsone as a product from an oxidation in vitro. Biochem Pharmacol. 1973 Jun 1;22(11):1383–1385. doi: 10.1016/0006-2952(73)90312-2. [DOI] [PubMed] [Google Scholar]
- Woosley R. L., Drayer D. E., Reidenberg M. M., Nies A. S., Carr K., Oates J. A. Effect of acetylator phenotype on the rate at which procainamide induces antinuclear antibodies and the lupus syndrome. N Engl J Med. 1978 May 25;298(21):1157–1159. doi: 10.1056/NEJM197805252982101. [DOI] [PubMed] [Google Scholar]