Dostert P, Strolin Benedetti M, Persiani S, La Croix R, Bosc M, Fiorentini F, Deffond D, Vernay D, Dordain G
1Pharmacia, Department of Pharmacokinetics and Metabolism, Milan, Italy.
J Neural Transm Suppl. 1995;45:247-57.
The addition of a dopamine agonist and of a monoamine oxidase type B inhibitor to I-dopa has been suggested in the therapy of Parkinson's disease. The plasma pharmacokinetics of both cabergoline and I-dopa have previously been shown to remain unaffected when the two drugs are given concomitantly. This study aimed at examining whether the plasma pharmacokinetic parameters of cabergoline and selegiline are modified when given in combination. Selegiline is hardly detectable in plasma. Therefore, the plasma levels of its metabolites amphetamine, methamphetamine and desmetylselegiline were used to assess the effect of cabergoline co-administration. Plasma levels of the selegiline metabolites were determined first after selegiline administration (10 mg/day) for 8 days, and then after administration of both drugs for 22 additional days (day 30). Cabergoline plasma levels were measured on day 30, and then after administration of cabergoline (1 mg/day) alone for further 22 days. No statistical difference was found between the Cmax.ss, tmax.ss, AUC0-24h.ss, C0h.ss, C24h.ss values of cabergoline and of the selegiline metabolites when the two drugs were given alone or in combination, indicating the absence of pharmacokinetic interaction between cabergoline and selegiline.
在帕金森病的治疗中，有人建议在左旋多巴治疗方案中添加多巴胺激动剂和单胺氧化酶B型抑制剂。先前研究表明，卡麦角林和左旋多巴同时给药时，二者的血浆药代动力学不受影响。本研究旨在探究卡麦角林和司来吉兰联合使用时，其血浆药代动力学参数是否会发生改变。司来吉兰在血浆中几乎检测不到。因此，通过检测其代谢产物苯丙胺、甲基苯丙胺和去甲基司来吉兰的血浆水平来评估卡麦角林联合用药的效果。首先，在司来吉兰（10毫克/天）给药8天后测定其代谢产物的血浆水平，然后在两种药物联合给药22天后（第30天）再次测定。在第30天测定卡麦角林的血浆水平，然后在单独给予卡麦角林（1毫克/天）22天后再次测定。单独给药或联合给药时，卡麦角林和司来吉兰代谢产物的Cmax.ss、tmax.ss、AUC0-24h.ss、C0h.ss、C24h.ss值均无统计学差异，表明卡麦角林和司来吉兰之间不存在药代动力学相互作用。
