title: Pharmacokinetics and pharmacodynamics of FK143, a nonsteroidal inhibitor of steroid 5 alpha-reductase, in healthy volunteers.
abstract: The pharmacokinetics and pharmacodynamics of FK143, a new nonsteroidal inhibitor of steroid 5 alpha-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-infinity)] 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-infinity) 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.
authors.affiliation: Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Katashima
authors.forename: T
authors.initials: T
authors.lastname: Irino
authors.forename: F
authors.initials: F
authors.lastname: Shimojo
authors.forename: A
authors.initials: A
authors.lastname: Kawamura
authors.forename: H
authors.initials: H
authors.lastname: Kageyama
authors.forename: N
authors.initials: N
authors.lastname: Higashi
authors.forename: Y
authors.initials: Y
authors.lastname: Miyao
authors.forename: Y
authors.initials: Y
authors.lastname: Tokuma
authors.forename: T
authors.initials: T
authors.lastname: Hata
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Sawada
authors.forename: T
authors.initials: T
authors.lastname: Iga
mesh_terms: D058891:5-alpha Reductase Inhibitors; D000284:Administration, Oral; D019540:Area Under Curve; D001798:Blood Proteins / Q000378:metabolism; D013196:Dihydrotestosterone / Q000097:blood; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D010654:Phenylbutyrates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011485:Protein Binding; D013997:Time Factors
chemical_list: C093354:4-(3-(3-(bis(4-isobutylphenyl)methylamino)benzoyl)-1H-indol-1-yl)butyric acid; D058891:5-alpha Reductase Inhibitors; D001798:Blood Proteins; D004791:Enzyme Inhibitors; D007211:Indoles; D010654:Phenylbutyrates; D013196:Dihydrotestosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D006854:Hydrocortisone