通过分阶剂量,不能避免Posaconazole-ibrutinib相互作用:在Posaconazole治疗期间如何优化ibrutinib剂量
Aleksi M Olkkola1,2, Tuija Tapaninen1,2,3,4, Aleksi Tornio5,6
1Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland.
British journal of clinical pharmacology
|October 23, 2023
概括
抗真菌药物波萨可纳显著增加了约10倍的易布鲁替尼暴露. 这种药物相互作用需要降低ibrutinib剂量,以防止在同时使用时出现潜在的毒性水平.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物相互作用 药物相互作用
- 药理动力学 药理动力学
背景情况:
- 易布鲁替尼是治疗B细胞恶性瘤的关键药物.
- 它通过CYP3A4的代谢导致可变的药理动力学和药物相互作用的高风险.
研究的目的:
- 为了研究ibrutinib和CYP3A4抑制剂pozaconazole之间的药理学相互作用.
- 为了确定波萨可纳时间 (早上与晚上) 对这种相互作用的影响.
主要方法:
- 进行了一项随机的,安慰剂控制的,三相交叉研究.
- 11名健康参与者接受了300毫克波萨康纳 (早上/晚上) 或安慰剂,随后是单剂量易布鲁替尼 (30,70或140毫克).
主要成果:
- 波萨可纳增加了易布鲁替尼暴露 (AUC0-∞) 约9.5至10.3倍,Cmax增加了8.2至8.5倍.
- 在早上和晚上服用波萨可纳之间没有观察到显著的差异.
- 代谢物PCI-45227与易布鲁替尼AUC0-∞的比率大幅降低.
结论:
- 波萨可纳会引起相当大的 (大约. 10倍) 的易布鲁丁尼布暴露增加.
- 分隔12小时的剂量并不能减轻这种相互作用.
- 为了避免毒性,当与波萨可纳同时使用时,每日易布鲁丁尼布剂量不应超过70毫克.
相关概念视频
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
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
Factors Affecting Protein-Drug Binding: Drug Interactions
173
Drug interactions are a critical aspect of pharmacology and can occur when two or more drugs compete for the same binding site. This competition can result in one drug displacing another, altering the effect of the displaced drug. Drug interactions are complex processes that rely heavily on how much of the displacer drug is present and how strongly it can bind to the same sites as the displaced drug.
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
173
Rational Dosage Regimen: Maintenance Dose and Loading Dose
4.1K
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...
4.1K
Hepatic Drug Clearance: Effect of Protein Binding
216
Hepatic clearance is influenced by protein binding based on the drug's extraction ratio. Drugs with high extraction ratios are considered flow-limited and remain unaffected by protein binding during hepatic clearance. On the other hand, drugs with low extraction ratios may be impacted by plasma protein binding, although the extent of this influence depends on the fraction of the drug bound.
For low-extraction-ratio drugs that are less than 80% protein-bound, minor changes in protein binding...
For low-extraction-ratio drugs that are less than 80% protein-bound, minor changes in protein binding...
216
Renal Failure: Dose Adjustments
97
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...
97


