Taylor A, Beerahee A, Citerone D, Davy M, Fitzpatrick K, Lopez-Gil A, Stocchi F
Drug Metabolism and Pharmacokinetics, SmithKline Beecham Pharmaceuticals, Welwyn, Herts, UK.
Br J Clin Pharmacol. 1999 Feb;47(2):219-22. doi: 10.1046/j.1365-2125.1999.00867.x.
The aim of this single-blind study was to assess the effect of ropinirole, a novel treatment for Parkinson's disease, on the steady-state pharmacokinetics and safety of digoxin in 10 patients with Parkinson's disease.
There were three parts to the study: digoxin once daily plus placebo three times daily for 1 week; digoxin once daily plus ropinirole three times daily for 6 weeks; and digoxin once daily plus placebo three times daily for 1 week. Serial blood samples were collected over 24 h at the end of each part of the study for pharmacokinetic assessment. Pre-dose blood samples were collected on specific days throughout the study to assess the attainment of steady-state plasma levels of digoxin. The primary endpoints were AUC(0, tau) and Cmax for digoxin.
There was a mean decrease of 10% in digoxin AUC (0, tau) (90% CI: 0.79, 1.01) and a 25% decrease in digoxin Cmax (90% CI: 0.58, 0.97) when ropinirole was co-administered, compared with digoxin alone Cmin plasma values for digoxin, however, were fairly constant throughout the study (point estimates 0.99, 95% CI: 0.85, 1.15). Changes in trough levels of digoxin are believed to be the most reliable way of assessing steady-state concentrations of digoxin, and therefore the clinical significance of an interaction. Changes in Cmax are too readily influenced by other factors.
These results therefore indicate that on pharmacokinetic grounds no dose adjustment is necessary for digoxin co-administered with ropinirole.
本单盲研究旨在评估一种治疗帕金森病的新药罗匹尼罗对10例帕金森病患者地高辛稳态药代动力学及安全性的影响。
本研究分为三个阶段：地高辛每日一次加安慰剂每日三次，共1周；地高辛每日一次加罗匹尼罗每日三次，共6周；地高辛每日一次加安慰剂每日三次，共1周。在研究各阶段结束时，于24小时内连续采集血样进行药代动力学评估。在研究期间的特定日期采集给药前血样，以评估地高辛稳态血药浓度的达到情况。主要终点为地高辛的AUC(0, tau)和Cmax。
与单独使用地高辛相比，联合使用罗匹尼罗时，地高辛的AUC(0, tau)平均降低了10%（90%可信区间：0.79, 1.01），Cmax降低了25%（90%可信区间：0.58, 0.97）。然而，地高辛的Cmin血浆值在整个研究过程中相当稳定（点估计值0.99，95%可信区间：0.85, 1.15）。地高辛谷浓度的变化被认为是评估地高辛稳态浓度以及相互作用临床意义的最可靠方法。Cmax的变化太容易受到其他因素的影响。
因此，这些结果表明，基于药代动力学原理，地高辛与罗匹尼罗联合使用时无需调整剂量。
