Pharmacokinetics of finrozole (MPV-2213ad), a novel selective aromatase inhibitor, in healthy men.
OBJECTIVE
To investigate the pharmacokinetics of finrozole (MPV-2213ad), a novel competitive aromatase enzyme inhibitor, in healthy male volunteers.


METHODS
The study was an open, partly randomized cross-over study including 23 volunteers receiving single doses of 3, 9 mg or 30 mg of finrozole as tablets or solution with 14 days between the administrations. The highest dose was given as tablets only. Serum concentrations of finrozole were determined using high performance liquid chromatography combined with mass spectrometry.


RESULTS
The mean time to peak serum concentration ranged from 2.5 to 3.1, and 0.6-0.7 h after tablets and solution, respectively. The Cmax values increased as the dose increased. The calculated apparent mean elimination half-life (t(1/2,z)) was approximately 3 h after the solution, and approximately 8 h after the tablet. The AUC(0,infinity) after finrozole tablets increased proportionally from 3 mg to 9 mg and from 3 to 30 mg. The calculated relative mean bioavailabilities (AUC(0,infinity)-ratio) for the 3 mg and 9 mg doses of finrozole as tablets were 89% and 78%, respectively.


CONCLUSIONS
The absorption of finrozole from the tablet formulation was relatively rapid, and the apparent elimination half-life was longer after the tablet than after the solution, probably reflecting overlap of the absorption with the elimination phase.
Ahokoski
O
O
Department of Pharmacology and Clinical Pharmacology, University of Turku and Clinical Pharmacology Unit, Turku University Central Hospital, FIN-20520 Turku, Finland. outi.ahokoski@utu.fi
Irjala
K
K
Taalikka
M
M
Manninen
P
P
Halonen
K
K
Kangas
L
L
Salminen
E
E
Huupponen
R
R
Scheinin
H
H
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D047072:Aromatase Inhibitors; D001682:Biological Availability; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004958:Estradiol / Q000378:metabolism; D006801:Humans; D008297:Male; D009570:Nitriles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012996:Solutions; D013607:Tablets; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D009570:Nitriles; D012996:Solutions; D013607:Tablets; D014230:Triazoles; C111409:finrozole; D004958:Estradiol