在慢性阶段的慢性髓性白血病中优化ponatinib的剂量
Françoise Huguet1,2, Delphine Réa2,3, Emilie Cayssials2,4
1Hematology Department, Institut Universitaire du Cancer, Centre Hospitalier Universitaire, Toulouse, France.
Expert review of hematology
|July 10, 2023
概括
这项研究提出了ponatinib的剂量策略,以平衡慢性髓性白血病患者的疗效和安全性. 决策树根据耐药性和分子反应优化剂量,旨在改善患者的治疗结果.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 心血管医学 心血管医学
背景情况:
- 波纳替尼对BCR-ABL1激酶突变具有强大作用,但具有心血管风险.
- 优化疗效/安全比对患者的益处至关重要.
- 现有的指导方针为慢性髓性白血病 (CML) 和心血管风险管理提供了信息.
研究的目的:
- 为选择ponatinib剂量提出一个决策树.
- 为了改善ponatinib治疗的疗效/安全概况.
- 为了指导临床医生在治疗CML患者时使用ponatinib.
主要方法:
- 对药理学数据和国际准则的审查.
- 对现实世界数据的分析和随机的II期试验.
- 开发基于患者个人资料的剂量算法.
主要成果:
- 将患者分为高耐药,低耐药和不耐药的组.
- 具体的起始和减少的每日剂量为每个类别提出.
- 剂量调整与治疗反应 (MR2,MR3) 和安全性相关.
结论:
- 拟议的决策树为ponatinib剂量提供了一个结构化的方法.
- 这一策略旨在最大限度地提高治疗效益,同时最大限度地降低心血管毒性.
- 基于耐药性和反应的个性化剂量是有效的CML管理的关键.
相关概念视频
Renal Failure: Dose Adjustments
123
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...
123
Combination Therapies and Personalized Medicine
4.9K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
206
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...
206
Dosage Regimen: Fixed Dose
1.9K
Fixed-dose regimens are a common approach to administer drugs to achieve and maintain desired levels of the drug in the body. In this dosing strategy, a specific amount of medication is given at regular intervals, often multiple times a day, to ensure a consistent drug concentration in the bloodstream.
Fixed-dose regimens can be used for various routes of administration, including intravenous (IV) injections and oral medications. For IV administration, a predetermined amount of the drug is...
Fixed-dose regimens can be used for various routes of administration, including intravenous (IV) injections and oral medications. For IV administration, a predetermined amount of the drug is...
1.9K
Drug Dosage Regimen: Overview
3.6K
A drug dosage regimen describes the specific instructions and schedule for administering a drug to a patient. It considers factors such as drug dosage, frequency, route of administration, and duration of treatment. Designing an appropriate dosage regimen for a patient aims to achieve a target drug concentration at the site of action.
Typically, the starting dose and dosing interval are guided by the manufacturer's recommendations based on clinical trials conducted during and after drug...
Typically, the starting dose and dosing interval are guided by the manufacturer's recommendations based on clinical trials conducted during and after drug...
3.6K
Nonlinear Pharmacokinetics: Overview
446
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...
446


