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

Clin Pharmacol Ther. 1998 Mar;63(3):354-66. doi: 10.1016/S0009-9236(98)90167-9.

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.

MeSH terms

  • 5-alpha Reductase Inhibitors*
  • Administration, Oral
  • Area Under Curve
  • Blood Proteins / metabolism
  • Dihydrotestosterone / blood
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology*
  • Follicle Stimulating Hormone / blood
  • Humans
  • Hydrocortisone / blood
  • Indoles / administration & dosage
  • Indoles / pharmacokinetics
  • Indoles / pharmacology*
  • Luteinizing Hormone / blood
  • Male
  • Middle Aged
  • Phenylbutyrates / administration & dosage
  • Phenylbutyrates / pharmacokinetics
  • Phenylbutyrates / pharmacology*
  • Protein Binding
  • Time Factors

Substances

  • 4-(3-(3-(bis(4-isobutylphenyl)methylamino)benzoyl)-1H-indol-1-yl)butyric acid
  • 5-alpha Reductase Inhibitors
  • Blood Proteins
  • Enzyme Inhibitors
  • Indoles
  • Phenylbutyrates
  • Dihydrotestosterone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Hydrocortisone