Pharmacokinetics and pharmacodynamics of FK143, a nonsteroidal inhibitor of steroid 5α-reductase, in healthy volunteers

• Published in: Clinical pharmacology and therapeutics 1998-03, Vol.63 (3), p.354-366
• Main Authors: Katashima, Masataka, Irino, Tadayoshi, Shimojo, Fumio, Kawamura, Akio, Kageyama, Hiromitu, Higashi, Naoko, Miyao, Yasuhiro, Tokuma, Yoji, Hata, Takehisa, Yamamoto, Koujirou, Sawada, Yasufumi, Iga, Tatsuji
• Format: Article
• Language: English
• Subjects: 5-alpha Reductase Inhibitors; Administration, Oral; Area Under Curve; Biological and medical sciences; Blood Proteins - metabolism; Dihydrotestosterone - blood; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - pharmacokinetics; Enzyme Inhibitors - pharmacology; Follicle Stimulating Hormone - blood; Genital system. Reproduction; Humans; Hydrocortisone - blood; Indoles - administration & dosage; Indoles - pharmacokinetics; Indoles - pharmacology; Luteinizing Hormone - blood; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Phenylbutyrates - administration & dosage; Phenylbutyrates - pharmacokinetics; Phenylbutyrates - pharmacology; Protein Binding; Time Factors
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1016/S0009-9236(98)90167-9

The pharmacokinetics and pharmacodynamics of FK143, a new nonsteroidal inhibitor of steroid 5α‐reductase, were investigated in healthy volunteers, with use of plasma FK143 concentrations and serum dihydrotestosterone levels as an index for pharmacologic effects. The area under the plasma concentration‐time curve from zero to infinity [AUC(0‐∞)] and maximum plasma concentration [Cmax] were increased dose proportionally after oral administration (100 to 500 mg) while subjects were in the fed state. The AUC(0‐∞) and Cmax after 500 mg oral administration during fed conditions were significantly larger than those during the fasted state, suggesting an increase of the absorption of FK143. Dihydrotestosterone concentrations after a single administration of FK143 (100 to 500 mg) during fed conditions decreased to about 65% of predose values and thereafter slowly recovered to the same levels as predose values at 168 hours. A combined pharmacokinetic‐pharmacodynamic model was constructed with use of changes in dihydrotestosterone concentrations. The pharmacokinetic‐pharmacodynamic profiles of FK143 after repeated administration were predictable with use of the pharmacokinetic‐pharmacodynamic parameters obtained after a single administration of FK143. Clinical Pharmacology & Therapeutics (1998) 63, 354–366; doi: