ファクターXI阻害剤の薬理学と臨床開発

Antonio Greco¹, Claudio Laudani¹, Marco Spagnolo¹

¹A.O.U. Policlinico "G. Rodolico - San Marco", University of Catania, Italy.

Circulation

|March 13, 2023

まとめ

抗凝固剤の戦略としては,FXIを標的とする.

科学分野:

薬理学と医学
血栓形成と血液静止の研究
薬物開発

背景:

血栓塞栓症の予防には抗凝固療法が不可欠ですが,出血のリスクを高めます.
現在の抗凝固剤は凝固のカスケードステップを阻害し,有効性と安全性の間のトレードオフにつながります.
ファクターXI (FXI) は,血栓増幅に重要な役割を果たしますが,血静性にはより少ない役割を果たします.

研究の目的:

FXI阻害剤の根拠,薬理,および臨床試験結果をレビューする.
抗血栓効果と出血リスクを分離するFXI抑制の可能性を調査する.
様々な臨床用薬におけるFXI阻害剤の将来の見通しについて議論する.

主な方法:

2期臨床試験を含むFXI阻害剤に関する既存の文献のレビュー
FXI阻害剤の異なるクラスとその作用機構の分析.
整形外科と心房細動の研究から得られた臨床データの検討

主要な成果:

2期試験では,FXI阻害剤は血栓性イベントを減少させても,血流を比例して増加させないことが示唆されています.
動脈動患者ではアサンデキサンの出血率がアピキサンの出血率より低かったが,脳卒中予防に関するデータは未定である.
FXI抑制は,末期腎疾患,脳卒中,心筋梗塞などの状態で研究されています.

結論:

FXIの抑制は,抗凝固薬の利益リスクプロフィールを改善する潜在的な治療戦略です.
FXI阻害剤の有効性と安全性を確認するために,さらなる大規模なフェーズ3試験が必要である.
FXI阻害剤の臨床における最適な役割と特定の用法は,まだ定義されていない.

キーワード:

抗凝固剤血液の凝固ファクターXI ヘモスタシストロンボシス

さらに関連する動画

13:08

Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay

Published on: September 9, 2012

19.0K

12:24

Helical Organization of Blood Coagulation Factor VIII on Lipid Nanotubes

Published on: June 3, 2014

12.4K

関連する概念動画

01:18

Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants

1.3K

Oral anticoagulants are vital tools in preventing and treating blood clotting disorders. This diverse class of medications can be categorized as vitamin K antagonists, exemplified by warfarin, and direct thrombin inhibitors (DTIs), such as dabigatran, as well as factor Xa inhibitors, including rivaroxaban.
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...

1.3K

01:30

Anticoagulant Drugs: Low-Molecular-Weight Heparins

795

Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...

795

01:11

Clinical Trials: Overview

3.1K

Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...

3.1K

01:29

Venous Thrombosis III: Interprofessional Care

Venous thrombosis requires effective prevention and treatment strategies to improve patient outcomes and reduce potential complications.Prevention StrategiesHealthcare providers must prioritize preventing venous thromboembolism (VTE) for all adult patients upon admission. Interventions depend on bleeding and thrombosis risk, medical history, current medications, diagnoses, planned procedures, and patient preferences. Patients on bed rest should change positions every two hours and, if not...

01:28

Preclinical Development: Overview

4.5K

Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...

4.5K

01:21

Factors Affecting Drug Response: Overview

2.0K

When it comes to infants and young children, they are typically administered smaller doses of medication in comparison to adults. This is primarily because their organ functions still need to fully develop, meaning their bodies are not as efficient at metabolizing or eliminating drugs. Additionally, their blood-brain barrier is more permeable than in adults. As a result, high concentrations of drugs can easily penetrate the central nervous system (CNS), potentially leading to neurological...