在接受血液透析的肥胖患者群体中,基于基于人群药理动力学模型的万科米辛加载剂量个性化
Lucie Polášková1, Jan Miroslav Hartinger2, Irena Murínová1,3
1Department of Clinical Pharmacy, Military University Hospital Prague, Prague, Czech Republic.
Journal of chemotherapy (Florence, Italy)
|June 18, 2024
概括
这项研究为肥胖的血液透析患者制定了万科米辛剂量策略. 基于模型的负载剂量确保了最佳的万科米辛暴露,针对基于AUC的药理动力学/药理动力学 (PK/PD) 目标.
科学领域:
- 药理动力学和药理动力学
- 腎臟病學 (nephrology) 是一種醫學專業.
- 传染性疾病 传染性疾病
背景情况:
- 肥胖症在药物剂量方面带来了挑战,特别是在血液透析患者中使用的抗生素,如万科米辛.
- 实现治疗范科米辛标 (AUC/MIC) 对于有效治疗和预防耐药性至关重要.
- 当前的剂量准则可能无法充分解决接受间歇性血液透析的肥胖患者的独特药理学特征.
研究的目的:
- 在间歇性血液透析的肥胖成年患者中开发一种万科米辛人群药理动力学模型.
- 提出基于模型的加载剂量策略,以实现基于AUC的推药理动力学/药理动力学 (PK/PD) 目标.
- 为了在这个特定的患者群体中优化万科米辛治疗.
主要方法:
- 对27名肥胖成年血液透析患者治疗药物监测数据的回顾性分析.
- 使用非线性混合效应建模开发一个人口药理动力学模型.
- 蒙特卡洛模拟以确定在48小时内实现PK/PD目标的最佳负载剂量.
主要成果:
- 瘦体质量 (LBM) 被确定为万科米辛分布体积 (Vd) 的显著共变量.
- 范科米辛清除 (CL) 与测试的变量没有相关性.
- 中位数Vd为68.4 L,中位数CL为0.86 L/h.
- 推的充满剂量范围在1500至2750毫克之间,根据LBM.
结论:
- 对于肥胖的血液透析患者,成功开发了一种万科米辛群体的药理动力学模型.
- 瘦身量是这个人群中万科米辛Vd的关键决定因素.
- 拟议的基于模型的加载剂量策略可以优化万科米辛的暴露,并改善PK/PD目标的实现.
相关概念视频
01:11Renal Failure: Dose Adjustments
80
In patients with renal impairment, drugs undergo significant changes in their pharmacokinetics, which require dosage adjustments to ensure safe and effective therapy.
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
80
01:15Two-Compartment Open Model: IV Infusion
218
A two-compartment model is a vital tool in pharmacokinetics, providing an essential understanding of drug behavior, especially for those administered via zero-order intravenous infusion. This model outlines two compartments: the central compartment, where elimination occurs, and the peripheral compartment.
The model illustrates the decrease in plasma drug concentration from the central compartment with a specific equation. It shows that under steady-state conditions, the drug's input rate...
The model illustrates the decrease in plasma drug concentration from the central compartment with a specific equation. It shows that under steady-state conditions, the drug's input rate...
218
01:24Rational Dosage Regimen: Maintenance Dose and Loading Dose
4.0K
A rational dosage regimen considers a drug's pharmacokinetics, including its absorption, distribution, metabolism, and elimination from the body. By understanding these factors, the appropriate dosage can be determined, and the dosing schedule can be designed to achieve and maintain the desired therapeutic effect while minimizing adverse effects.
In most cases, drugs are administered repetitively or infused continuously to maintain a steady-state concentration in the body. At a steady...
In most cases, drugs are administered repetitively or infused continuously to maintain a steady-state concentration in the body. At a steady...
4.0K
01:12Analysis of Population Pharmacokinetic Data
252
Analysis of population pharmacokinetic data involves studying the behavior of drugs within diverse populations to understand their pharmacokinetic parameters. Traditional pharmacokinetic methods typically involve collecting samples from a few individuals and estimating these parameters. While these methods are commonly used, they have limitations in capturing the variability in drug response among individuals or heterogeneous populations. Population pharmacokinetics is employed to address these...
252
01:09One-Compartment Model: IV Infusion
188
Intravenous (IV) infusion is often utilized when continuous and controlled drug delivery is necessary, such as during surgery or in the treatment of chronic diseases. This method offers numerous advantages, including immediate drug action, precise control over dosage, and bypassing the first-pass metabolism.
The one-compartment model for IV infusion uses mathematical equations to describe the rate of change in drug quantity in the body. At steady-state or infusion equilibrium, the drug input...
The one-compartment model for IV infusion uses mathematical equations to describe the rate of change in drug quantity in the body. At steady-state or infusion equilibrium, the drug input...
188
01:09One-Compartment Open Model for IV Bolus Administration: Estimation of Elimination Rate Constant, Half-Life and Volume of Distribution
238
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...
238