对基于模型的IVIVC的观点,用于开发皮下注射剂
Clairissa D Corpstein1, Tonglei Li2
1Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana, USA.
Pharmaceutical research
|July 31, 2023
概括
开发通用皮下药物需要更好的临床前测试和体外-体内相关性 (IVIVC) 指导. 机械建模和模拟可以优化配方设计,加快这些流行的注射药物产品的开发.
科学领域:
- 药理动力学和药物输送方法
- 在制药领域的计算建模.
背景情况:
- 皮下药物管理越来越多地用于小分子和大分子.
- 皮下注射剂的通用开发受到缺乏特定的临床前测试和体外与体内相关性 (IVIVC) 准则的阻碍.
- 现有的IVIVC方法,通常是为口服药物开发的,可能无法充分解决皮下注射部位生理学和药物吸收.
研究的目的:
- 审查目前IVIVC对口服药物的指导方针.
- 讨论IVIVC对皮下药物产品的独特挑战.
- 突出机械,计算建模的潜力,以支持皮下注射开发.
主要方法:
- 对口服药品的现有IVIVC指南的文献综述.
- 分析口服和皮下途径之间的生理和药理动力学差异.
- 探索用于配方设计和IVIVC的机械建模和模拟方法.
主要成果:
- 目前IVIVC对口服药物的框架对于皮下注射药物是不够的.
- 皮下药物释放和吸收受到复杂的注射部位因素的影响.
- 机械建模可以识别影响皮下药物释放的关键药物和配方属性.
结论:
- 正式化的临床前测试和IVIVC指导对于推动通用皮下药物开发至关重要.
- 计算建模和模拟提供了一个强大的方法来克服目前在配方设计和皮下注射剂IVIVC的局限性.
- 将建模和模拟集成到现有的IVIVC策略中,可以加速皮下注射产品的开发.
相关概念视频
One-Compartment Open Model for IV Bolus Administration: General Considerations
248
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,...
248
Two-Compartment Open Model: IV Bolus Administration
576
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...
576
One-Compartment Open Model for IV Bolus Administration: Estimation of Clearance
104
Clearance is a key pharmacokinetic parameter that quantifies the volume of body fluid from which a drug is entirely removed within a specific time frame. It is crucial in assessing how a drug is eliminated from the body and has critical clinical applications.
In the one-compartment open model for intravenous (IV) bolus administration, clearance is estimated by dividing the elimination rate by the plasma drug concentration. This equation leverages the elimination rate constant and the apparent...
In the one-compartment open model for intravenous (IV) bolus administration, clearance is estimated by dividing the elimination rate by the plasma drug concentration. This equation leverages the elimination rate constant and the apparent...
104
Two-Compartment Open Model: IV Infusion
274
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...
274
One-Compartment Open Model for IV Bolus Administration: Estimation of Elimination Rate Constant, Half-Life and Volume of Distribution
335
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...
335
One-Compartment Model: IV Infusion
229
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...
229


