Ahokoski O, Irjala K, Taalikka M, Manninen P, Halonen K, Kangas L, Salminen E, Huupponen R, Scheinin H
Department of Pharmacology and Clinical Pharmacology, University of Turku and Clinical Pharmacology Unit, Turku University Central Hospital, FIN-20520 Turku, Finland.
Br J Clin Pharmacol. 2001 Dec;52(6):702-4. doi: 10.1046/j.0306-5251.2001.01488.x.
To investigate the pharmacokinetics of finrozole (MPV-2213ad), a novel competitive aromatase enzyme inhibitor, in healthy male volunteers.
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.
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.
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.
研究新型竞争性芳香化酶抑制剂非诺唑（MPV - 2213ad）在健康男性志愿者体内的药代动力学。
本研究为开放性、部分随机交叉研究，纳入23名志愿者，他们分别接受3mg、9mg或30mg的非诺唑片剂或溶液单剂量给药，给药间隔为14天。最高剂量仅以片剂形式给药。采用高效液相色谱 - 质谱联用测定非诺唑的血清浓度。
片剂和溶液给药后，血清浓度达峰的平均时间分别为2.5至3.1小时和0.6 - 0.7小时。Cmax值随剂量增加而升高。溶液给药后计算得出的表观平均消除半衰期（t(1/2,z)）约为3小时，片剂给药后约为8小时。非诺唑片剂的AUC(0,∞)从3mg增至9mg以及从3mg增至30mg时均呈比例增加。3mg和9mg剂量的非诺唑片剂计算得出的相对平均生物利用度（AUC(0,∞) - 比值）分别为89%和78%。
非诺唑片剂的吸收相对较快，片剂给药后的表观消除半衰期长于溶液给药后，这可能反映了吸收与消除相的重叠。
