Pharmacokinetics and safety of repirinast tablets in healthy Chinese subjects

ABSTRACT Repirinast is a new, synthetic, disodium cromoglycate-like antiallergic agent for oral administration in humans. This study evaluated the safety, tolerability and pharmacokinetics of repirinast tablets in healthy Chinese volunteers. This was a phase I, open-label, randomized, single- and multiple-dose study. Subjects were assigned to receive a single dose of repirinast tablet at either 150, 300, or 450 mg, or multiple doses of 150 mg twice daily for 5 days. Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of active metabolite MY-1250 (deesterified repirinast) were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 0.75 hour, and the mean t1/2 was approximately 16.21 hours. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 150 to 450 mg. In the multiple-dose study, the steady-state was reached within 3 days with no accumulation. Repirinast tablet was well tolerated in healthy Chinese subjects.

摘要：雷吡那司特（Repirinast）是一种新型合成的、类似色甘酸钠的口服抗过敏剂，用于人类口服给药。本研究评估了雷吡那司特片在健康中国志愿者中的安全性、耐受性和药代动力学特征。本研究为一项I期开放标签随机单剂量及多剂量临床试验。受试者被分配接受150mg、300mg或450mg的雷吡那司特片单剂量给药，或每日两次150mg、连续5天的多剂量给药。采用液相色谱-串联质谱法（LC-MS/MS）对血浆样本进行分析。采用WinNonlin软件通过非房室分析法计算活性代谢物MY-1250（雷吡那司特的去酯代谢物）的药代动力学参数。采用SPSS软件进行统计学分析。所有不良事件（AEs）均为轻度且持续时间有限，未观察到严重不良事件（SAE）、死亡或受试者退出研究。在单剂量给药研究中，峰浓度（Cmax）约于0.75小时达到，平均半衰期（t₁/₂）约为16.21小时。曲线下面积（AUC）与峰浓度（Cmax）随剂量升高而增加，但在150mg至450mg剂量范围内未观察到剂量比例性。在多剂量给药研究中，受试者于3天内达到稳态且无药物蓄积。雷吡那司特片在健康中国受试者中耐受性良好。