Palovaara Sanna, Anttila Markku, Nyman Leena, Laine Kari
The Department of Pharmacology and Clinical Pharmacology, University of Turku, Pharmacity, It. Pitkäkatu 4, 20510 Turku, Finland.
Eur J Clin Pharmacol. 2002 Jul;58(4):259-63. doi: 10.1007/s00228-002-0469-y. Epub 2002 May 22.
The aim of this study was to investigate the effect of hormone-replacement therapy (HRT) on the pharmacokinetics of the selective monoamine oxidase B inhibitor selegiline and its primary metabolites desmethylselegiline and l-metamphetamine.
In this randomised, double-blind, cross-over trial, 12 healthy female subjects received once daily for 10 days either HRT containing 2 mg estradiol valerate and 250 microg levonorgestrel or matched placebo. On day 10, they took a single 10-mg oral dose of selegiline. The serum concentrations of selegiline, desmethylselegiline and metamphetamine were measured for 32 h.
There was a 59% difference ( P=0.14) in the area under the serum concentration-time curve (AUC) of selegiline during the HRT compared with the placebo phase, but only a little or no concomitant reduction in the AUC of desmethylselegiline (-7%, P=0.071) or metamphetamine (2%, P=0.614) was observed. Maximum plasma concentration (C(max)) of selegiline was not changed, but a small, statistically significant, reduction in the C(max) of desmethylselegiline (-17%, P=0.03) was seen during the HRT phase. The C(max) of methamphetamine was slightly but not significantly reduced (-5%, P=0.06). The unchanged AUC ratios of desmethylselegiline/selegiline and metamphetamine/selegiline indicate that the primary metabolism of selegiline was not affected by HRT. All study treatments were well tolerated.
Unlike oral contraceptives, HRT is not likely to have clinically significant pharmacokinetic interaction with selegiline.
本研究旨在探讨激素替代疗法（HRT）对选择性单胺氧化酶B抑制剂司来吉兰及其主要代谢产物去甲基司来吉兰和l-甲基苯丙胺药代动力学的影响。
在这项随机、双盲、交叉试验中，12名健康女性受试者连续10天每天接受一次含2mg戊酸雌二醇和250μg左炔诺孕酮的HRT或匹配的安慰剂。在第10天，她们口服10mg单剂量的司来吉兰。测量司来吉兰、去甲基司来吉兰和甲基苯丙胺的血清浓度32小时。
与安慰剂阶段相比，HRT期间司来吉兰血清浓度-时间曲线下面积（AUC）有59%的差异（P=0.14），但去甲基司来吉兰（-7%，P=0.071）或甲基苯丙胺（2%，P=0.614）的AUC仅略有降低或未降低。司来吉兰的最大血浆浓度（C(max)）未改变，但在HRT阶段去甲基司来吉兰的C(max)有小幅、统计学上显著的降低（-17%，P=0.03）。甲基苯丙胺的C(max)略有降低但无统计学意义（-5%，P=0.06）。去甲基司来吉兰/司来吉兰和甲基苯丙胺/司来吉兰的AUC比值不变，表明司来吉兰的主要代谢未受HRT影响。所有研究治疗耐受性良好。
与口服避孕药不同，HRT不太可能与司来吉兰发生具有临床意义的药代动力学相互作用。
