Multiple dose pharmacokinetics of fiduxosin under fasting conditions in healthy elderly male subjects.
Selective alpha1a-adrenoceptor antagonists are effective agents for treatment of benign prostatic hyperplasia, a disorder occurring in middle-aged and elderly males. The objective of this study was to determine the pharmacokinetics of fiduxosin, a novel alpha1a-adrenoceptor antagonist, following multiple dose administration. This was carried out in a Phase I, randomized, double-blind, placebo-controlled, parallel group, multiple oral dose study of fiduxosin. Single once-daily oral doses of 30, 60, 90 or 120 mg of fiduxosin or placebo were administered to healthy elderly male subjects (n = 48; 8 active and 4 placebo per dosing group) for 14 consecutive days. Fiduxosin plasma concentration-versus-time profiles for days 1, 7 and 14 were used to assess fiduxosin pharmacokinetics. Steady state was achieved by day 7. At steady-state mean Tmax (time to maximum plasma concentration), CL/F (apparent oral clearance) and Vbeta/F (apparent volume of distribution) ranges were 1.8-7.8 h, 27.3-47.2 L h(-1) and 846-1399 L, respectively. Tmax and VbetaF were independent of dose. Cmax (maximum plasma concentration), Cmin (minimum plasma concentration) and AUC24 (area under plasma concentration vs time curve from 0 to 24 h) for days 7 and 14 were linearly proportional with dose overthe 30-120 mg/day dose range and were unchanged from day 7 to day 14. It was concluded that fiduxosin multiple-dose pharmacokinetics were dose-independent and time-invariant over the 30-120 mg/day dose range under fasting conditions.
Dutta
Sandeep
S
Clinical Pharmacokinetics, Abbott Laboratories, Abbott Park, IL 60064-6104, USA. Sandeep.Dutta@abbott.com
Zhang
Yiming
Y
Daszkowski
Daniel J
DJ
Granneman
G Richard
GR
Verlinden
Marleen
M
D000284:Administration, Oral; D018674:Adrenergic Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D058668:Adrenergic alpha-1 Receptor Antagonists; D000368:Aged; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005215:Fasting / Q000378:metabolism*; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011744:Pyrimidinones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018340:Receptors, Adrenergic, alpha-1
C547713:ADRA1A protein, human; D018674:Adrenergic Antagonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D006575:Heterocyclic Compounds, 3-Ring; D011744:Pyrimidinones; D018340:Receptors, Adrenergic, alpha-1; C447622:fiduxosin