年龄和同时服用药物的影响在儿科患者的杜洛特格拉维尔葡萄化
Tom G Jacobs1, Hylke Waalewijn1,2, Lily Houlden3
1Department of Pharmacy, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, The Netherlands.
British journal of clinical pharmacology
|September 4, 2024
概括
儿童的多卢特格拉维尔 (DTG) 代谢表现出与成人相似的代谢比率. 利芬素显著增加了这一比率,突出了其在小儿艾滋病毒患者同时服用的重要性.
科学领域:
- 药理学 药理学是指药理学的学科.
- 艾滋病毒/艾滋病研究研究
- 儿科医学 儿科医学
背景情况:
- 多卢特格拉维尔 (DTG) 是艾滋病毒治疗的关键抗逆转录病毒药物.
- DTG主要通过尿素二酸糖转移酶被代谢成不活性葡萄糖化物代谢物 (DTG-gluc).
- 了解杜洛特格拉维尔代谢比率 (DTG-MR) 对于优化儿科艾滋病毒治疗至关重要.
研究的目的:
- 在接受DTG的3个月至18岁儿童中,描述多洛特格拉维尔代谢比率 (DTG-MR).
- 评估包括年龄,体重,NRTI骨干,利芬素使用和功能在内的因素对DTG-MR的影响.
- 将儿科DTG-MR与成人数据进行比较,并为未来的药理动力学建模提供信息.
主要方法:
- 在85名来自CHAPAS-4和ODYSSEY试验的儿童中对DTG-MR (DTG-gluc AUC0-24h / DTG AUC0-24h) 的分析.
- 使用多重线性回归来评估各种共变量对DTG-MR的影响.
- 收集和分析了药理动力学数据,以确定代谢比率及其影响因素.
主要成果:
- 儿童的整体几何平均值DTG-MR为0.054 (52%CV),与成人值相比.
- 利芬素的使用是影响DTG-MR的唯一显著因素 (P < .001).
- 与未服用瑞芬素的儿童相比,接受瑞芬素的儿童的DTG-MR高出1.81倍.
结论:
- 儿科DTG-MR与成年人相似,并不受年龄或NRTI骨干的显著影响.
- 利芬素的同时使用在儿童中大大增加了DTG-MR.
- 这些发现支持将成人药理动力学数据推断到儿科患者群体,并指导治疗策略.
相关概念视频
Factors Affecting Drug Response: Overview
1.9K
When it comes to infants and young children, they are typically administered smaller doses of medication in comparison to adults. This is primarily because their organ functions still need to fully develop, meaning their bodies are not as efficient at metabolizing or eliminating drugs. Additionally, their blood-brain barrier is more permeable than in adults. As a result, high concentrations of drugs can easily penetrate the central nervous system (CNS), potentially leading to neurological...
1.9K
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
104
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...
104
Phase II Reactions: Glucuronidation
319
Glucuronidation, a pivotal phase II biotransformation process, involves the coupling of glucuronic acid to a drug or xenobiotic. Given its widespread occurrence and critical role in drug metabolism, it's considered the most crucial phase II reaction. It enhances the water solubility of substances, aiding their expulsion from the body. The driving force behind these reactions is a group of enzymes known as UDP-glucuronosyltransferases (UGTs). UGTs facilitate the transfer of a glucuronic acid...
319
Drug Metabolism: Phase II Reactions
3.7K
Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
3.7K
Factors Affecting Drug Biotransformation: Biological
128
Biological factors significantly impact drug metabolism, influencing drug clearance, efficacy, and potential toxicity.
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
128
Factors Influencing Drug Absorption: Pharmaceutical Parameters
123
Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
123


