在功能下降的患者中,伊米佩内姆剂量不足:全球临床药理动力学研究
Anh Quan Truong1, Tim J L Smeets2, Jean Terrier3
1Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands; Rotterdam Clinical Pharmacometrics Group, Rotterdam, The Netherlands; National Drug Information and Adverse Drug Reaction Monitoring Centre, Hanoi University of Pharmacy, Hanoi, Vietnam.
概括
标准的伊米佩内姆剂量可能无法在患有功能障碍的重症患者中达到治疗目标. 可能需要更高的剂量来有效治疗Pseudomonas aeruginosa感染,特别是在较高的最小抑制度 (MIC) 时.
科学领域:
- 药理动力学和药理动力学
- 传染性疾病 传染性疾病
- 腎臟病學 (nephrology) 是一種醫學專業.
背景情况:
- 对伊米佩内姆的群体药动力学 (popPK) 模型对于优化重症患者的剂量至关重要.
- 现有的模型往往不能充分代表这些患者功能的广泛范围.
- 这项研究通过评估不同功能水平的伊米佩内姆剂量来弥补这一差距.
研究的目的:
- 评估标准伊米佩内姆疗程在患有不同程度功能的重症患者中达到的目标.
- 利用人口药理动力学建模和模拟来预测药物暴露.
- 在更广泛的患者群体中为 imipenem 提供最佳剂量策略的信息.
主要方法:
- 使用来自瑞士的数据开发了一个popPK模型,并与来自捷克和越南的数据进行验证.
- 采用蒙特卡洛模拟来确定实现目标的概率 (PTA) 和累积反应率 (CFR).
- 研究的目标是40%和100%的自由药物度超过针对Pseudomonas aeruginosa的最低抑制度 (ƒT>MIC),流行病学切断值为4mg/L,在一系列肌素清除 (CLCRCG) 值中.
主要成果:
- 在研究地点,显著比例的患者 (46.4-57.9%) 患有功能下降 (eGFRCKD-EPI<90 mL/min).
- 肌素清除率 (CLCRCG) 是影响伊米佩内姆清除率的一个重要因素.
- 虽然所有疗法都达到MIC ≤ 2 mg/L的40% ƒT > MIC目标,但在功能下降的患者中,没有一种疗法在敏感的Pseudomonas aeruginosa (MIC ≤ 4 mg/L) 中达到100% ƒT > MIC.
结论:
- 标签上的伊米佩内姆剂量方案不足以实现100%的 ƒT>MIC目标 (4 mg/L) 在患有功能受损的危急病患者中.
- 可能需要增加伊米佩内姆剂量,以有效治疗由Pseudomonas aeruginosa引起的感染,其MIC为4mg/L.
- 需要进行进一步的研究,以探索这种患者群体中基于模型准确剂量的疗效,安全性和潜力.
相关概念视频
01:11Renal Failure: Dose Adjustments
69
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...
69
01:17Factors Affecting Renal Clearance: Renal Impairment
62
Renal dysfunction significantly impairs the renal clearance of drugs, leading to potential complications in drug therapy. Renal failure, which can be caused by various factors, poses a significant challenge in the elimination of drugs from the body.
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
62
01:22Renal Drug Excretion: Effect of Urine pH, Flow Rate, and Drug pKa
145
The pH of urine, the drug's pKa, and the urine flow rate are vital parameters for drug reabsorption and excretion. Urinary pH varies between 4.6 and 8.0 and is influenced by diet, drug intake, and the patient's pathophysiology. It affects a drug's ionization state and reabsorption. For instance, carbohydrate-rich food produces alkaline urine promoting drug excretion, while proteins and certain medications like ascorbic acid lead to acidic urine enhancing reabsorption.
The pKa of a...
The pKa of a...
145
01:21Factors 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
01:09Factors Affecting Renal Clearance: Drug Distribution and Drug Interactions
108
Renal clearance plays a pivotal role in drug elimination from the body and can be influenced by drug distribution and interactions. Understanding these factors is crucial in pharmacology as they impact the effectiveness and duration of drug therapy.
One important factor is the relationship between renal clearance and the apparent volume of distribution. Renal clearance tends to be inversely proportional to the apparent volume of distribution. Drugs with an extensive distribution volume or those...
One important factor is the relationship between renal clearance and the apparent volume of distribution. Renal clearance tends to be inversely proportional to the apparent volume of distribution. Drugs with an extensive distribution volume or those...
108
01:22Drug Elimination by Renal Route: Tubular Reabsorption
3.3K
During the process of renal excretion, as the glomerular filtrate progresses to the distal convoluted tubule (DCT), drugs that are highly permeable, lipophilic, and nonionized undergo passive reabsorption from the tubular fluid into the surrounding peritubular capillaries. This reabsorption process restricts their elimination through the kidneys. However, the majority of drugs are either weak acids or weak bases, and their ionization level is dependent on pH. By altering the pH of urine, the...
3.3K