Abstract

Objective: This study evaluated and compared the safety, pharmacokinetics, and pharmacodynamics of regadenoson injection (test) and regadenoson original injection (Lexiscan, reference) in healthy Chinese subjects.
Materials and methods: In a randomized, positive-control, single-center, single-dose study, 24 healthy Chinese subjects were divided into test and reference groups (12 subjects each). Subjects in the test group received a single bolus of test drug (0.4 mg/5 mL), while the reference group received the same dose of reference drug. Blood and urine samples were collected before and after drug administration, and regadenoson concentrations were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Results: No serious adverse events (AEs) occurred. There was no significant difference in the incidence of adverse reactions between the two preparations. The pharmacokinetic parameters, including maximum concentration (C_max), the area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC_0–t), and the area under the concentration-time curve from time 0 to infinity (AUC_0–∞), were assessed to compare the pharmacokinetic of two regadenoson preparations. The test/reference geometric mean ratios of C_max, AUC_0–t, and AUC_0–∞ were 102.84, 99.16, and 99.77%, respectively. The 90% confidence intervals (CIs) of AUC_0–t and AUC_0–∞ fell within 0.8 – 1.25, but the 90% CIs of C_max did not. Blood pressure (BP) and heart rate (HR) were measured to compare the pharmacodynamics of the two preparations. The test and reference drugs had similar HR responses (63.22 ± 38.45% vs. 37.50 ± 16.96%), systolic BP response (4.81 ± 13.73% vs. –3.83 ± 12.29%), and diastolic BP response (–7.75 ± 12.84% vs. –16.13 ± 9.85%), p > 0.05. After adjusting the weight of males and females, there were significant differences in C_max, AUC_0–t, AUC_0–∞, T_1/2, V_ss, λ_z, Ae%, p < 0.05.
Conclusion: The test drug demonstrated similar pharmacokinetic and pharmacodynamic characteristics as the reference drug. Additionally, it was well-tolerated and safe in healthy Chinese participants. Sex may influence regadenoson pharmacokinetics.

Author Details

Authors

• Yi Liu¹
• Cao-Yang Wang¹
• Hai-Wen Wang¹
• Ming-Qing Xu¹
• Hong-Wen Zhang¹
• Li-Jun Xie¹
• Juan Chen¹
• Chen Zhou¹
• Lu-Ning Sun^{1, 2}
• Yong-Qing Wang^{1, 2}

Departments

• ¹ Research Division of Clinical Pharmacology, First Affiliated Hospital with Nanjing Medical University, and
• ² School of Pharmacy, Nanjing Medical University, Nanjing, China

Address

Yong-Qing Wang, PhD
or
Lu-Ning Sun, PhD
Research Division of Clinical Pharmacology
First Affiliated Hospital of Nanjing Medical University
300 Guangzhou Road, Nanjing 210009, China
Email: [email protected]; [email protected]

Citation