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

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.