埃多克萨班在儿科患者中的群体药理动力学和药理动力学
Peng Zou1, Akhilesh Atluri2, Peter Chang2
1Quantitative Clinical Pharmacology, Daiichi Sankyo Inc., Basking Ridge, New Jersey, USA.
CPT: pharmacometrics & systems pharmacology
|November 11, 2024
概括
这项研究对儿科患者的edoxaban的药理动力学和药理动力学进行了表征. 儿童的暴露与成年人相似,eGFR,体重和年龄影响了变化.
科学领域:
- 药理学 药理学是指药理学的学科.
- 儿科药理动力学 儿科药理动力学
- 药物的新陈代谢和消除.
背景情况:
- 埃多克萨班是一种口服激活X因子 (FXa) 抑制剂.
- 了解其在儿童群体中的药理动力学 (PK) 和药理动力学 (PD) 概况对于安全有效的使用至关重要.
- 在PK/PD中个体间的变异性需要共变量分析.
研究的目的:
- 在儿科患者中描述edoxaban的PK和PK-PD关系.
- 为了确定影响edoxaban PK可变性的共变量.
- 为了比较儿科和成人PK/PD数据.
主要方法:
- 使用了人口PK/PD建模.
- 一个带有过境隔间的两间隔间模型描述了儿科PK.
- 分析了包括估计膜过率 (eGFR),体重和月经后年龄在内的共变量.
主要成果:
- 儿科edoxaban PK受EGFR,体重和月经后年龄的影响.
- 成熟被纳入清除计算.
- 模拟的儿科暴露量与成人剂量 (每天60毫克) 相当.
- 建立了PK-PD模型 (对抗FXa的Emax,对aPTT/PT的线性).
- 探索性分析发现,疗效/安全事件与因有限事件而引起的暴露之间没有相关性.
结论:
- 在儿科患者中,EDOXABAN的PK/PD可以使用人口建模来预测.
- 像eGFR和年龄这样的共变量是理解变异性的关键.
- 儿科用剂量策略可以通过与成人数据的比较来指导.
相关概念视频
Factors Affecting Drug Response: Overview
1.9K
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...
1.9K
Nonlinear Pharmacokinetics: Bioavailability and Protein-Drug Binding
126
When a drug follows nonlinear pharmacokinetics, its bioavailability, the amount of the drug that reaches the systemic circulation, can change with different doses. This is due to the presence of a saturable pathway. The pathway becomes saturated as the drug concentration increases, decreasing the absorption rate. Consequently, the drug's bioavailability may be lower than expected at higher doses.
To quantify the extent of bioavailability, pharmacologists often use a parameter called .
To quantify the extent of bioavailability, pharmacologists often use a parameter called .
126
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
87
The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
A study on guinea pigs examined the...
87
Nonlinear Pharmacokinetics: Overview
282
Nonlinear or dose-dependent pharmacokinetics is a phenomenon that occurs when the pharmacokinetic parameters of certain drugs deviate from linear pharmacokinetics at higher doses. These drugs do not follow the expected first-order kinetics, where the rate of drug elimination is directly proportional to the drug concentration. Instead, they exhibit a nonlinear relationship, which can be attributed to several factors.
Nonlinearity can arise due to the saturation of plasma protein-binding or...
Nonlinearity can arise due to the saturation of plasma protein-binding or...
282
Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
1.2K
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...
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...
1.2K
Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis
49
Noncompartmental analyses offer an alternative method for describing drug pharmacokinetics without relying on a specific compartmental model. In this approach, the drug's pharmacokinetics are assumed to be linear, with the terminal phase log-linear. This assumption allows for simplified analysis and interpretation of the drug's behavior in the body.
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...
49


