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.

中文翻译：

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支持在移植中使用更昔洛韦治疗药物监测的证据。

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影响。研究了围绕通过治疗药物监测 (TDM) 优化药物剂量的证据和挑战，并提出了建议。最新发现 当前剂量指南的药代动力学研究表明，GCV 浓度存在较高的个体间和个体内变异性。这有时与某些移植受者中巨细胞病毒（CMV）病毒载量的缓慢下降有关。GCV 相关骨髓抑制的高发生率限制了该药物在移植环境中的使用。确定可从 GCV TDM 中受益的患者群体包括儿科患者、肺移植的囊性纤维化患者、肾移植的肥胖患者以及肾功能波动或正在进行血液透析的患者。难治性巨细胞病毒的出现，特别是在免疫功能低下的患者中，凸显了这些抗病毒药物适当剂量的重要性。需要考虑宿主遗传因素，最近有两个宿主基因被证明可以解释更昔洛韦治疗期间患者间的变异。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，从而有可能改善病毒学和临床结果。然而，支持在临床实践中使用 TDM 的证据仍然有限，需要在移植队列中进行进一步研究。摘要 需要进一步研究新型生物标志物来指导预防和治疗中的目标浓度。在移植受者中使用 TDM 可能会提高现有抗病毒药物的临床疗效并优化移植受者的预后。