HORMONAL EFFECTS, TOLERABILITY, AND PRELIMINARY KINETICS IN MEN OF MK-906, A 5-ALPHA-REDUCTASE INHIBITOR

被引:28
作者
DESCHEPPER, PJ
IMPERATOMCGINLEY, J
VANHECKEN, A
DELEPELEIRE, I
BUNTINX, A
CARLIN, J
GRESSI, MH
STONER, E
机构
[1] Department of Pharmacology and Clinical Pharmacology, University of Leuven, School of Medicine, Leuven
[2] Cornell University Medical College, New York, NY
[3] Merck Sharp and Dohme Research Laboratories, Rahway, NJ
关键词
STEROIDS; 5-ALPHA-REDUCTASE INHIBITOR; PHARMACODYNAMICS; DIHYDROTESTOSTERONE; TESTOSTERONE; HUMAN; PHARMACOKINETICS; FINASTERIDE;
D O I
10.1016/0039-128X(91)90003-E
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The hormonal effects following the acute (single dose) administration of a 4-azasteroid inhibitor of 5-alpha-reductase (MK-906) were evaluated in 10 healthy male volunteers. Marked suppression of serum dihydrotestosterone (DHT) was observed after the administration of single doses as low as 12.5 mg. The mean percent decrease in DHT at 24 hours in the group treated with a single 25-mg dose was 56% +/- 10% compared with the baseline. The suppression of plasma DHT levels continued for up to 72 hours. This study demonstrates that administration of single oral doses (12.5 to 400 mg) of MK-906 results in a significant decrease in the conversion of testosterone to DHT.
引用
收藏
页码:469 / 471
页数:3
相关论文
共 8 条
  • [1] Rasmusson, Liang, Brooks, A new class of 5α-reductase inhibitors, Gene Regulation by Steroid Hormones II, pp. 311-334, (1983)
  • [2] Liang, Heiss, Cheung, Reynolds, Rasmusson, 4-Azasteroidal 5α-reductase inhibitors without affinity for the androgen receptor, J Biol Chem, 259, pp. 734-739, (1984)
  • [3] Liang, Cascieri, Cheung, Reynolds, Rasmusson, Species differences in prostatic steroid 5α-reductase of rat, dog, and human, Endocrinology, 177, pp. 571-579, (1985)
  • [4] Imperato-McGinley, Guerrero, Gautier, Peterson, Steroid 5α-reductase in man. An inherited form of male pseudohermaphroditism, Science, 186, pp. 1213-1215, (1974)
  • [5] Peterson, Imperato-McGinley, Gautier, Sturla, Male pseudohermaphroditism due to steroid 5α-reductase deficiency, Am J Med, 62, pp. 170-191, (1977)
  • [6] Imperato-McGinley, Peterson, Gautier, Sturla, Male pseudohermaphroditism secondary to 5α-reductase deficiency A model for the role of androgens in both the development of the male phenotype and the evolution of a male gender identity, Journal of Steroid Biochemistry, 2, pp. 637-645, (1979)
  • [7] Carlin, Christofalo, Vanden Heuvel, High performance liquid Chromatographie determination of N-(2-methyl-2-propyl)-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide, a 4-aza-steroid, in human plasma from a phase I study, J Chromatogr, 427, pp. 79-91, (1988)
  • [8] Stoner, The clinical development of a 5α-reductase inhibitor, Finasteride, Proceedings of the XIV Meeting of the International Study Group for Steroid Hormones, 37, pp. 375-378, (1990)