Preliminary pharmacokinetics and metabolism of novel non-steroidal antiandrogens in the rat: Relation of their systemic activity to the formation of a common metabolite

  title={Preliminary pharmacokinetics and metabolism of novel non-steroidal antiandrogens in the rat: Relation of their systemic activity to the formation of a common metabolite},
  author={D. Cousty-Berlin and B. Bergaud and M. Bruyant and T. Battmann and C. Branche and D. Philibert},
  journal={The Journal of Steroid Biochemistry and Molecular Biology},
The non-steroidal antiandrogens, RU 58841 and RU 56187 are amongst the most active of a new series of N-substituted aryl hydantoins or thiohydantoins. Their pharmacokinetics and principal metabolic profiles have been evaluated in rat plasma after intravenous administration of a 10 mg/kg dose. Both compounds disappear relatively rapidly from the plasma (elimination half-life of the order of 1 h), but they form a common metabolite, the N-desalkyl derivative, RU 56279, which is eliminated much… Expand
Pharmacological profile of RU 58642, a potent systemic antiandrogen for the treatment of androgen-dependent disorders
RU 58642 proved to be significantly more potent than the reference compounds in reducing prostate weight: 3-30 times orally and 3-100 times subcutaneously, and thus the most potent antiandrogen to date to the authors' knowledge. Expand
Development of fluridil, a topical suppressor of the androgen receptor in androgenetic alopecia
Nonsteroidal antiandrogens (AA) cannot be topically used for androgenetic alopecia (AGA) because of systemic resorption. A new class of androgen receptor (AR) suppressors designed for safe topicalExpand
Design and synthesis of an androgen receptor pure antagonist (CH5137291) for the treatment of castration-resistant prostate cancer.
A series of 5,5-dimethylthiohydantoin derivatives synthesized and evaluated for androgen receptor pure antagonistic activities for the treatment of castration-resistant prostate cancer indicated that CH5137291 was a potent AR pure antagonist which did not produce the agonist metabolite. Expand
Pharmacokinetics and Pharmacodynamics of Nonsteroidal Androgen Receptor Ligands
This review focuses on the pharmacokinetics, metabolism, and pharmacology of clinically used and emerging nonsteroidal AR ligands, including antagonists, agonists, and selective androgen receptor modulators. Expand
Synthesis and structure-activity investigation of iodinated arylhydantoins and arylthiohydantoins for development as androgen receptor radioligands.
A series of side-chain derivatives of the arylhydantoin RU 58841 and the arylthiohydantoin RU 59063, wherein the aromatic trifluoromethyl group was replaced with iodine, was synthesized for possibleExpand
Fluridil, a Rationally Designed Topical Agent for Androgenetic Alopecia: First Clinical Experience
Topical fluridil is nonirritating, nonsensitizing, nonresorbable, devoid of systemic activity, and anagen promoting after daily use in most AGA males. Expand
A controlled study of the effects of RU58841, a non‐steroidal antiandrogen, on human hair production by balding scalp grafts maintained on testosterone‐conditioned nude mice
Human hair growth can be monitored for several months after the transplantation of scalp samples from men with androgen‐dependent alopecia on to female nude mice to study the effect of a new non‐steroidal antiandrogen – RU 58841 – on human hair growth. Expand
Novel ligands of steroid hormone receptors
The development of novel ligands for steroid hormone receptors has become a burgeoning field with tremendous potential in numerous human therapies, and these compounds will likely grow into complementary pharmacophores of defined function and enhanced therapeutic utility. Expand
Local Inhibition of Sebaceous Gland Growth by Topically Applied RU 58841
The potent localized inhibition of sebaceous glands by RU 58841 demonstrates the excellent potential of this compound as a topical drug for the treatment of acne and other androgen-mediated disorders. Expand
Nonsteroidal anti-androgens and selective androgen receptor modulators having a pyridyl moiety
Compounds having the following structure or a salt thereof, prostate cancer, benign prostatic hyperplasia, polycystic ovarian syndrome, acne, hirsutism, seborrhea, androgenic alopecia, male patternExpand


Non-steroidal antiandrogens: Synthesis and biological profile of high-affinity ligands for the androgen receptor
The results suggest that these new compounds may be useful as specific markers for the androgen receptor as well as for the treatment of androgen-dependent diseases or disorders such as prostate cancer, acne, hirsutism and male pattern baldness. Expand
Pharmacokinetics and metabolismof nilutamide
It can be concluded that in humans, unlike other species, plasma decay of nilutamide is very slow and elimination is almost exclusively by metabolism. Expand
ICI 176,334: a novel non-steroidal, peripherally-selective antiandrogen.
  • B. Furr
  • Biology, Medicine
  • Progress in clinical and biological research
  • 1988
A new non-steroidal antiandrogen ICI 176,334 (4'-cyano-3-(4-fluorophenylsulphonyl)-2-hydroxy-2-methyl-3'- trifluoromethyl)propion-anilide) has now been discovered which causes regression of the accessory sex organs but does not increase serum concentrations of LH and androgens. Expand
RU 58841, a new specific topical antiandrogen: A candidate of choice for the treatment of acne, androgenetic alopecia and hirsutism
The results suggest that RU 58841 might useful for the topical treatment of androgen-dependent skin disorders such as acne, androgenetic alopecia and hirsutism. Expand
The pure antiandrogen ru 23908 (anandron®), a candidate of choice for the combined antihormonal treatment of prostatic cancer: A review
The nonsteroidal antiandrogen RU 23908 (AnandronR) weakly interacts with the prostatic cytosolic androgen receptor and shows a fast dissociation rate. When administered to immature castrated rats upExpand
Antiandrogens: Clinical applications
In advanced prostatic carcinoma antiandrogens represent a good alternative to estrogen therapy with less side effects and in combination with surgical or medical castration (LH-RH analogues) achieve a complete androgen blockade. Expand
use of Metabolite AUC Data in Bioavailability Studies to Discriminate Between Absorption and First-Pass Extraction
  • M. Weiss
  • Chemistry, Medicine
  • Clinical pharmacokinetics
  • 1990
The aim of the presenticle is to demonstrate the application of this method by a retrospective analysis of relevant data available In the literature, based on the clearance approach, which is valid for linear phannacoklnelic and renal elimination of the drug. Expand
A Multiple Comparison Procedure for Comparing Several Treatments with a Control
(1955). A Multiple Comparison Procedure for Comparing Several Treatments with a Control. Journal of the American Statistical Association: Vol. 50, No. 272, pp. 1096-1121.