Galapagos Biotech Limited, Cambridge, UK.
Quotient Sciences, Nottingham, UK.
Clin Pharmacol Drug Dev. 2022 Feb;11(2):246-256. doi: 10.1002/cpdd.1021. Epub 2021 Oct 11.
Ziritaxestat is a novel inhibitor of autotaxin, an enzyme responsible for the production of lysophosphatidic acid, the downstream signaling of which mediates responses to tissue injury and has been implicated in the pathogenesis of fibrotic conditions such as idiopathic pulmonary fibrosis and systemic sclerosis. This study (Clinical Trial Registration: NCT03787186) was designed to assess the absorption, distribution, metabolism, and excretion of orally administered 600-mg ziritaxestat labeled with a carbon-14 tracer ( C-ziritaxestat). To understand the absolute bioavailability of ziritaxestat, an intravenous 100-μg microdose, labeled with a microtracer amount of C radiation, was administered in a separate part of the study, following an unlabeled 600-mg therapeutic oral dose of ziritaxestat. Six healthy male subjects completed each study part. The majority of the labeled oral dose was recovered in feces (77%), with a total mass balance of 84%. The absolute bioavailability of ziritaxestat was 54%. Ziritaxestat was the main (76%) circulating drug-related product. There were 7 treatment-emergent adverse events, all of which were considered mild and not considered to be related to the study drug.
齐立他汀是一种新型的自分泌酶抑制剂，可抑制自分泌酶的产生，自分泌酶可产生溶血磷脂酸，其下游信号转导可介导组织损伤反应，并与特发性肺纤维化和系统性硬皮病等纤维化疾病的发病机制有关。这项研究（临床试验注册：NCT03787186）旨在评估口服给予 600mg 碳-14 标记齐立他汀（ C-齐立他汀）后的吸收、分布、代谢和排泄。为了了解齐立他汀的绝对生物利用度，在研究的另一部分中，给予了静脉内 100μg 的微剂量，用微量 C 辐射标记，随后给予了未标记的齐立他汀 600mg 治疗口服剂量。6 名健康男性受试者完成了每个研究部分。标记的口服剂量大部分在粪便中回收（77%），总质量平衡为 84%。齐立他汀的绝对生物利用度为 54%。齐立他汀是主要（76%）的循环药物相关产物。有 7 种治疗相关的不良事件，均为轻度，与研究药物无关。
