时间变化的隔间模型捕捉了大鼠中万科米消除动学的小时尺度变化
Matthew H McDonough1,2, Julian Gerson3,4, Tod Kippin3,4
1Department of Statistics and Applied Probability, University of California Santa Barbara, Santa Barbara, California, 93106, USA.
British journal of pharmacology
|March 28, 2025
概括
在老鼠中,抗生素万科米的药理动力学可以在几小时内显著改变. 时间变化的模型比标准模型更好地描述这些快速的药理动力学变化.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药理动力学 药理动力学
- 药物新陈代谢 药物新陈代谢
背景情况:
- 传统的药理动力学评估使用稀疏的数据,对所有受试者的平均值.
- 在体内传感器现在允许在个体中收集时间密集的数据.
- 以前的研究表明,托布拉米辛的快速药理动力学变化.
研究的目的:
- 在老鼠中分析时间密集的万科米辛的药理动力学数据.
- 调查时间变化的模型是否比标准模型更好地描述万科米辛的药理动力学.
主要方法:
- 使用先前从六只麻醉的老鼠收集的时间密集的血度测量.
- 标准配备的一间或两间隔间的车型.
- 适应时间变化的单个分区模型来评估统计偏好.
主要成果:
- 时间变化的单间模型在统计学上是五个六个vancomycin时间课程的首选.
- 在去除了分布阶段效应后,在五个数据集中的四个中,更喜欢采用相互时间变化的模型.
- 证明了对考虑到时间变化消除的模型的统计偏好.
结论:
- 提供了动物模型证据,证明清药物的显著药物动力学变异性.
- 突出指出,这些药理动力学变化可以在短时间内 (小时) 发生.
- 建议某些药物的传统药理动力学建模的局限性.
相关概念视频
Compartment Models: Single-Compartment Model
The single-compartment model serves as a simplified representation of the human body. This model assumes that the body functions as a single, well-mixed open compartment. When a drug is administered intravenously, it enters the body and quickly distributes uniformly. The drug then undergoes biotransformation and elimination, ultimately leaving the body. The volume of this compartment is referred to as the apparent volume of distribution into which the drug can uniformly distribute. In this...
Compartment Models: Two-Compartment Model
The two-compartment model divides the body into central and peripheral compartments to account for varying blood perfusion rates among organs and tissues, affecting drug distribution. The central compartment includes blood and highly perfused tissues with rapid drug distribution, while the peripheral compartment contains tissues with slower drug distribution. After a single IV bolus dose, the drug concentration is high in plasma and low in tissues. The drug distribution between compartments...
Clearance Models: Compartment Models
Clearance measures drug elimination from the central compartment, including plasma and highly perfused organs like kidneys and liver. Its calculation varies depending on pharmacokinetic models and administration routes. The one-compartment model, for instance, portrays the pharmacokinetics of polar drugs such as aminoglycoside antibiotics administered intravenously and readily excreted in urine. In this case, clearance is influenced by the terminal rate constant (λz) and the total volume of...
One-Compartment Open Model for IV Bolus Administration: Estimation of Elimination Rate Constant, Half-Life and Volume of Distribution
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 from...
Two-Compartment Open Model: IV Bolus Administration
The two-compartment model for intravenous (IV) bolus administration illustrates drug distribution in the body, subdividing it into central and peripheral compartments. This model operates on the concept of two-compartment kinetics. The drug's plasma concentration shows a bi-exponential decline following IV bolus administration, signaling the presence of two disposition processes: distribution and elimination.
The disparity between drug input and the sum of drug transfer rates between...
The disparity between drug input and the sum of drug transfer rates between...
Two-Compartment Open Model: Extravascular Administration
The two-compartment model for extravascular administration represents a drug's absorption and distribution process. It features a central compartment, where the drug is first absorbed, and a peripheral compartment, which illustrates the drug's distribution throughout the body. The rate of change in drug concentration in the central compartment is calculated by three exponents: absorption, distribution, and elimination.
The absorption exponent (ka) indicates the speed at which the drug is...
The absorption exponent (ka) indicates the speed at which the drug is...


