Pharmacokinetics and Safety of Long-Acting Release Formulations of Pasireotide (SOM230) in a Male Population Who Are Hyperendemic Hepatitis B/C and Chronic Kidney Disease: An Open-Label, Phase I Study.

IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Chun-Jui Huang, Chieh-Hua Lu, Kuang-Chung Shih
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引用次数: 0

Abstract

Background: In patients with kidney or hepatic diseases, an increment of circulating pasireotide is also expected. Therefore, this open-label, phase I study aimed to evaluate the pharmacokinetic profiles and safety of subcutaneous (SC) and long-acting release (LAR) intramuscular injections of pasireotide in male Taiwanese volunteers who are hyperendemic hepatitis B/C and chronic kidney disease (CKD).

Methods: A total of 45 male volunteers were randomized to receive one of nine treatment sequences, involving a single subcutaneous injection of 300, 600, or 900 μg pasireotide, a multiple SC injection of the same dosage of pasireotide [300, 600, or 900 μg, twice daily (b.i.d.) for 4 days and a single dose for 1 day], and a single dose of 20, 40, or 60 mg LAR pasireotide intramuscular injection. The pasireotide SC and LAR formulations were prepared and supplied to the study center by Novartis. Pharmacokinetic parameters were assessed from both formulations. All adverse events that occurred in participants throughout the study period, including abnormalities in fasting levels of glucose, insulin, and glucagon, as well as laboratory measurements and electrocardiograms, were recorded.

Results: Analysis of plasma concentration over time revealed a rapid absorption of pasireotide, with a maximal concentration at 0.5 h after SC injection(s) of pasireotide (300-900 µg). Following a single dose of pasireotide LAR (20-60 mg), a sustained release was observed following an initial increase on day 1, a plateau around day 20, and a decline over the next 7 weeks.

Conclusions: Both pasireotide formulations showed dose-proportional pharmacokinetics and 300-900 μg of SC pasireotide and 20-60 mg LAR pasireotide treatment showed favorable safety profiles and was well-tolerated when administered in male Taiwanese volunteers who are hyperendemic hepatitis B/C and CKD.

Abstract Image

帕西核苷酸长效释放制剂(SOM230)在高地方性乙型肝炎/丙型肝炎和慢性肾脏疾病男性人群中的药代动力学和安全性:一项开放标签的I期研究。
背景:在肾脏或肝脏疾病患者中,循环帕西核苷酸也会增加。因此,这项开放标签的I期研究旨在评估帕西核苷酸皮下(SC)和长效释放(LAR)肌肉注射在患有乙型肝炎/丙型肝炎和慢性肾脏疾病(CKD)的台湾男性志愿者中的药代动力学特征和安全性,包括单次皮下注射300、600或900μg帕西核苷酸,多次SC注射相同剂量的帕西核苷酸[300、600或90μg,每日两次(b.i.d.),持续4天,单次剂量持续1天],以及单次剂量20、40或60 mg LAR帕西核苷酸肌内注射。帕西核苷酸SC和LAR制剂由诺华公司制备并提供给研究中心。对两种制剂的药代动力学参数进行了评估。记录整个研究期间参与者发生的所有不良事件,包括空腹血糖、胰岛素和胰高血糖素水平异常,以及实验室测量和心电图。结果:随着时间的推移,血浆浓度分析显示帕西核苷酸吸收迅速,SC注射帕西核苷酸(300-900µg)0.5小时后达到最大浓度。在单剂量的帕西核苷酸LAR(20-60mg)之后,在第1天的初始增加、第20天左右的平稳期之后观察到持续释放,结论:两种帕西核苷酸制剂均显示出剂量比例的药代动力学,300-900μg SC帕西核苷酸和20-60 mg LAR帕西核苷酸治疗显示出良好的安全性,在患有高流行性乙型肝炎/丙型肝炎和CKD的台湾男性志愿者中给药时耐受性良好。
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来源期刊
CiteScore
3.70
自引率
0.00%
发文量
64
审稿时长
>12 weeks
期刊介绍: Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences. Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.
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