第1阶段研究评估了皮下注射levothyroxine sodium (XP-8121) 的药理动力学,剂量相称性,生物可用性和耐受性
Richard Fitch1, Diane R Mould2, Valentina Conoscenti1
1Xeris Pharmaceuticals, Inc., Chicago, Illinois, USA.
Clinical and translational science
|May 10, 2025
概括
一种新的皮下勒沃西注射 (XP-8121) 显示剂量比例性和与口服形式相似的安全性. 这种皮下利沃甲状腺素配方可能为甲状腺功能低下症的治疗提供一种替代方案,并有可能每周服用一次.
科学领域:
- 药理学 药理学是指药理学的学科.
- 内分泌学 在内分泌学.
- 药物开发 药物开发
背景情况:
- 利沃甲状腺素是治疗甲状腺功能低下症的标准治疗方法,通常是口服 (PO).
- 由于吸收,食物和药物相互作用,口服甲的药理动力学 (PK) 可能是可变的.
- XP-8121是一种新型的皮下 (SC) 甲氧素注射配方,正在第三阶段开发中.
研究的目的:
- 与口服Levothyroxine相比,XP-8121 SC的PK和剂量比例的特征.
- 为了评估XP-8121SC的安全性和耐受性.
- 利用人口PK (PPK) 建模来告知未来的发展.
主要方法:
- 第1阶段,对健康成年人的两部分研究.
- 第1部分:随机交叉研究,比较XP-8121 SC剂量与口服勒沃西.
- 第2部分:评估较高XP-8121 SC剂量和剂量比例的单期研究.
主要成果:
- XP-8121 SC的吸收速度比口服levothyroxine要慢,水平持续4-5天.
- 对XP-8121SC的剂量相称性在测试剂量中得到证实.
- 在XP-8121 SC和口服勒沃西组之间,安全性和耐受性概况相似.
结论:
- XP-8121 SC显示出可预测的药理动力学和剂量相称性.
- PPK建模表明,每周使用XP-8121 SC剂量 (每天4次口服剂量) 可以达到类似的稳定状态暴露.
- XP-8121 SC显示出作为另一种用于levothyroxine治疗的注射途径的希望.
相关概念视频
Clinical Trials: Overview
2.6K
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...
2.6K
Preclinical Development: Overview
4.2K
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...
4.2K
One-Compartment Open Model for IV Bolus Administration: Estimation of Elimination Rate Constant, Half-Life and Volume of Distribution
161
The one-compartment open model is a simplified approach used in pharmacokinetics to understand the distribution and elimination of a drug administered through an intravenous bolus. This model assumes rapid drug dispersal throughout the body and elimination using a first-order process. Key pharmacokinetic parameters, such as the elimination rate constant (k), half-life (t1/2), and the apparent volume of distribution (Vd), can be estimated from this model. The elimination rate is calculated...
161
Clinical Trials
6.6K
Clinical trials are prospective experimental studies conducted on humans to determine the safety and efficacy of treatments, drugs, diet methods, and medical devices. Using statistics in clinical trials enables researchers to derive reasonable and accurate conclusions from the collected data, allowing them to make wise decisions in uncertain situations. In medical research, statistical methods are crucial for preventing errors and bias.
There are four phases in a clinical trial. A phase one...
There are four phases in a clinical trial. A phase one...
6.6K
Drug Administration and Therapy Phases: Overview
402
Drugs, the chemical agents used in diagnosing, treating, or preventing diseases, undergo a four-phase process of development: pharmaceutic, pharmacokinetics, pharmacodynamics, and therapeutic.
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
402
One-Compartment Open Model for IV Bolus Administration: General Considerations
142
The one-compartment model is a pharmacokinetic tool that models the body as a single, uniform compartment, facilitating the understanding of drug distribution and elimination. This model is particularly beneficial for intravenous (IV) bolus administration, where the drug rapidly circulates throughout the body.
The drug's presence in the body is defined by an equation representing the difference between the rates of drug entry and exit. Key parameters—elimination rate constant,...
The drug's presence in the body is defined by an equation representing the difference between the rates of drug entry and exit. Key parameters—elimination rate constant,...
142


