Pharmacokinetic profile of ivabradine hemisulfate sustained‐release tablets administered in Chinese healthy volunteers: An open‐label, randomized, single‐dose, three‐period crossover study

摘要

Abstract We aimed to determine the pharmacokinetics and safety of three single oral doses (5, 10 and 15?mg) of ivabradine hemisulfate sustained‐release tablets in healthy Chinese volunteers. A total of 12 volunteers (six males and six females) were randomized to receive a single oral dose of ivabradine hemisulfate sustained‐release tablets 5, 10 or 15?mg, with a 1‐week washout between periods. Blood samples were collected at regular intervals from 0 to 48 h after drug administration, and the concentrations of ivabradine and N ‐desmethyl ivabradine were determined by HPLC–tandem mass spectrometry. Pharmacokinetic parameters were estimated by non‐compartmental analysis. After administering single doses of 5, 10 and 15?mg, the mean maximum concentration ( C max ) levels of ivabradine were 4.36, 7.29 and 12.62?ng/mL, and the mean area under the curve from time 0 to 48 h ( AUC 0–48 ) values were 55.66, 101.16 and 182.09?h·ng/mL, respectively. The mean C max levels of N ‐desmethyl ivabradine were 1.05, 2.03 and 3.16?ng/mL, and the mean AUC 0–48 values were 20.61, 39.44 and 65.72?h·ng/mL, respectively. The median time of maximum concentration ( T max ) levels of ivabradine and N ‐desmethyl ivabradine were 5?h for all three doses tested. The pharmacokinetic properties of ivabradine hemisulfate sustained‐release tablets were linear at doses from 5 to 15?mg. Ivabradine hemisulfate sustained‐release tablet appears to be well tolerated in these healthy volunteers.