支持在移植中使用更昔洛韦治疗药物监测的证据。

IF 3.6 3区 医学 Q2 INFECTIOUS DISEASES Current Opinion in Infectious Diseases Pub Date : 2023-12-01 Epub Date: 2023-09-19 DOI:10.1097/QCO.0000000000000965
Diana D Wong, Su Ann Ho, Ana Domazetovska, Michelle K Yong, William D Rawlinson
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引用次数: 1

摘要

综述目的:本综述描述了目前对更昔洛韦(GCV)和缬更昔洛韦(ValGCV)药代动力学/药效学特征的了解,强调了宿主遗传因素对患者间变异性的可能贡献。研究了通过治疗药物监测(TDM)优化药物给药的证据和挑战,并提出了建议。最近的发现:当前给药指南的药代动力学研究表明,GCV浓度在个体间和个体内具有很高的变异性。这有时与一些移植受者的巨细胞病毒载量缓慢下降有关。GCV相关骨髓抑制的高发病率限制了该药物在移植环境中的使用。确定受益于GCV TDM的患者群体包括儿童患者、肺移植后的囊性纤维化患者、肾移植后的肥胖患者以及肾功能波动或正在进行血液透析的患者。难治性耐药CMV的出现,特别是在免疫受损的患者中,突出了适当给药这些抗病毒药物的重要性。需要考虑宿主遗传因素,最近有两个宿主基因被证明是更昔洛韦治疗期间患者间变异的原因。治疗药物监测已被证明可以提高抗病毒目标水平的实现。TDM的使用可以指导基于浓度的剂量调整,有可能改善病毒学和临床结果。然而,支持TDM在临床实践中使用的证据仍然有限,需要在移植队列中进行进一步研究。总结:需要对新的生物标志物进行进一步的研究,以指导预防和治疗中的目标浓度。在移植受者中使用TDM可能会提高目前抗病毒药物的临床疗效,并优化移植受者的结果。
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Evidence supporting the use of therapeutic drug monitoring of ganciclovir in transplantation.

Purpose of review: This review describes current knowledge of ganciclovir (GCV) and valganciclovir (ValGCV) pharmacokinetic/pharmacodynamic characteristics, highlighting the likely contribution from host genetic factors to interpatient variability. The evidence and challenges surrounding optimization of drug dosing through therapeutic drug monitoring (TDM) are examined, with recommendations made.

Recent findings: Pharmacokinetic studies of current dosing guidelines have shown high interindividual and intraindividual variability of GCV concentrations. This is sometimes associated with a slow decline in cytomegalovirus (CMV) viral load in some transplant recipients. A high incidence of GCV-associated myelosuppression has limited the use of this drug in the transplant setting. Patient groups identified to benefit from GCV TDM include pediatric patients, cystic fibrosis with lung transplantation, obese with kidney transplantation, and patients with fluctuating renal function or on hemodialysis. The emergence of refractory resistant CMV, particularly in immune compromised patients, highlights the importance of appropriate dosing of these antivirals. Host genetic factors need to be considered where recently, two host genes were shown to account for interpatient variation during ganciclovir therapy. Therapeutic Drug Monitoring has been shown to improve target antiviral-level attainment. The use of TDM may guide concentration-based dose adjustment, potentially improving virological and clinical outcomes. However, evidence supporting the use of TDM in clinical practice remains limited and further study is needed in the transplant cohort.

Summary: Further studies examining novel biomarkers are needed to guide target concentrations in prophylaxis and treatment. The use of TDM in transplant recipients is likely to improve the clinical efficacy of current antivirals and optimize outcomes in transplant recipients.

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来源期刊
CiteScore
6.70
自引率
2.60%
发文量
121
审稿时长
6-12 weeks
期刊介绍: This reader-friendly, bimonthly resource provides a powerful, broad-based perspective on the most important advances from throughout the world literature. Featuring renowned guest editors and focusing exclusively on two topics, every issue of Current Opinion in Infectious Disease delivers unvarnished, expert assessments of developments from the previous year. Insightful editorials and on-the-mark invited reviews cover key subjects such as HIV infection and AIDS; skin and soft tissue infections; respiratory infections; paediatric and neonatal infections; gastrointestinal infections; tropical and travel-associated diseases; and antimicrobial agents.
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