基因多态性和癌症恶病质对接受阿片类镇痛药的患者中纳尔地定药代动力学和肠蠕动的影响。

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY Fundamental & Clinical Pharmacology Pub Date : 2024-01-08 DOI:10.1111/fcp.12976
Emi Nakatsugawa, Takafumi Naito, Kaito Shibata, Ryo Kitajima, Junichi Kawakami
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引用次数: 0

摘要

背景/目的:晚期癌症患者对纳尔灭定的临床反应因人而异。这是一项前瞻性、单中心、观察性研究,旨在评估基因多态性和恶病质状态对血浆纳尔地定和临床反应的影响:方法:研究纳入了48名正在接受纳尔地定治疗的患者,这些患者在治疗癌痛的过程中因阿片类药物引起便秘。结果:癌症患者的基因型、恶病质状态和临床反应有很大差异:结果:癌症患者血浆中纳尔灭定的浓度变化很大,且与血清总蛋白水平相关。CYP3A5*3等位基因患者的血浆中纳尔灭定浓度高于*1等位基因患者。本研究中检测的 ABCB1 基因型与血浆中纳尔灭定的浓度无关。血浆中纳尔灭定的浓度与 4β- 羟基胆固醇的水平呈负相关。难治性恶病质患者的血浆纳尔德美汀浓度低于先兆性恶病质和恶病质患者。虽然难治性恶病质患者血清中的白细胞介素-6(IL-6)和急性期蛋白水平较高,但它们与血浆中的萘美汀无关。结论:血浆中纳尔灭定、CYP3A5*3/*3的浓度较高,以及在开始使用阿片类镇痛药后较早服用纳尔灭定与肠蠕动的改善有关:结论:在癌症患者CYP3A5活性不足的情况下,血浆中纳尔灭定的含量会增加。血清IL-6较高的癌症患者血浆中纳尔灭定的含量较低。与CYP3A5基因型有关的血浆纳尔地美定和纳尔地美定的开始使用时间与肠蠕动的改善有关。
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Impacts of genetic polymorphisms and cancer cachexia on naldemedine pharmacokinetics and bowel movements in patients receiving opioid analgesics

Background/Objectives

Clinical responses to naldemedine vary between individuals with advanced cancer. This is a prospective, single-center, observational study aimed to evaluate the influence of genetic polymorphisms and cachexia status on plasma naldemedine and clinical responses.

Methods

Forty-eight patients being treated with naldemedine for opioid-induced constipation under treatment of cancer pain were enrolled. Plasma naldemedine concentrations were determined on the fourth day or later after administration of naldemedine, and the associations with genotypes, cachexia status, and clinical responses were assessed.

Results

Cancer patients exhibited a large variation in the plasma naldemedine concentrations, and it was correlated with serum total protein level. Patients who were homozygous CYP3A5*3 had a higher plasma concentration of naldemedine than those with the *1 allele. ABCB1 genotypes tested in this study were not associated with plasma naldemedine. A negative correlation was observed between the plasma naldemedine concentration and 4β-hydroxycholesterol level. The plasma naldemedine concentration was lower in patients with refractory cachexia than in those with precachexia and cachexia. While serum levels of interleukin-6 (IL-6) and acute-phase proteins were higher in patients with refractory cachexia, they were not associated with plasma naldemedine. A higher plasma concentration of naldemedine, CYP3A5*3/*3, and an earlier naldemedine administration after starting opioid analgesics were related to improvement of bowel movements.

Conclusion

Plasma naldemedine increased under deficient activity of CYP3A5 in cancer patients. Cachectic patients with a higher serum IL-6 had a lower plasma naldemedine. Plasma naldemedine, related to CYP3A5 genotype, and the initiation timing of naldemedine were associated with improved bowel movements.

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来源期刊
CiteScore
5.30
自引率
6.90%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.
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