Department of Clinical Pharmacy, Division of Pulmonary Sciences and Critical Care, University of Colorado, Aurora, Colorado 80045, USA.
J Heart Lung Transplant. 2012 Feb;31(2):159-66. doi: 10.1016/j.healun.2011.11.016.
Valganciclovir is commonly used for cytomegalovirus prevention after lung transplantation. The pharmacokinetic profile of valganciclovir in lung transplant patients has not been well described or linked to efficacy and safety.
This prospective, randomized, crossover study determined the steady-state pharmacokinetic profile of 2 different doses of valganciclovir in lung transplant recipients and compared these profiles with intravenous ganciclovir.
Ten patients were evaluated. Patients were 56.8 ± 3.4 years old and had a mean creatinine clearance of 69 ± 9 ml/min. Oral bioavailability of ganciclovir after administration of valganciclovir was 59%, and mean half-life was 3.73 ± 1.15 hours. The maximal concentration after intravenous 5 mg/kg ganciclovir was significantly higher than after 450 mg valganciclovir (8.37 ± 3.03 mg/liter vs. 5.3 ± 2.09 mg/liter, respectively; p = 0.02) and similar to 900 mg valganciclovir (7.93 ± 3.97 mg/liter; p = 0.78). A higher area under the curve at 0-24 hours (AUC(0-24)) was found with 900 mg valganciclovir compared with intravenous 5 mg/kg/day ganciclovir (47.8 ± 19.7 vs 32.9 ± 10.8 mg · hour/liter, respectively; p = 0.049). The AUC(0-24) for 450 mg valganciclovir twice daily was 45.5 ± 22.9 mg · hour/liter.
Valganciclovir at 900 mg/day resulted in the equivalent of a mean daily dose of 7.7 mg/kg intravenous ganciclovir. Higher systemic ganciclovir exposures occurred after 900 mg/day valganciclovir compared with intravenous 5 mg/kg/day ganciclovir. Valganciclovir therapeutic drug monitoring may be warranted in select lung transplant patients to avoid increased toxicity.
更昔洛韦常用于肺移植后的巨细胞病毒预防。肺移植患者更昔洛韦的药代动力学特征尚未得到很好的描述，也与疗效和安全性无关。
这项前瞻性、随机、交叉研究确定了肺移植受者两种不同剂量更昔洛韦的稳态药代动力学特征，并将这些特征与静脉用更昔洛韦进行了比较。
共评估了 10 名患者。患者年龄为 56.8 ± 3.4 岁，平均肌酐清除率为 69 ± 9 ml/min。给予更昔洛韦后，更昔洛韦的口服生物利用度为 59%，平均半衰期为 3.73 ± 1.15 小时。静脉给予 5mg/kg 更昔洛韦后，最大浓度明显高于静脉给予 450mg 更昔洛韦（分别为 8.37 ± 3.03mg/l 和 5.3 ± 2.09mg/l；p = 0.02），与静脉给予 900mg 更昔洛韦相似（7.93 ± 3.97mg/l；p = 0.78）。与静脉给予 5mg/kg/天的更昔洛韦相比，给予 900mg 更昔洛韦时发现 0-24 小时的 AUC（0-24）更高（分别为 47.8 ± 19.7 和 32.9 ± 10.8mg·小时/l；p = 0.049）。每日两次给予 450mg 更昔洛韦的 AUC（0-24）为 45.5 ± 22.9mg·小时/l。
每天 900mg 更昔洛韦的剂量相当于平均 7.7mg/kg 静脉用更昔洛韦的剂量。与静脉给予 5mg/kg/天的更昔洛韦相比，每天给予 900mg 更昔洛韦后，全身更昔洛韦暴露量增加。在某些肺移植患者中，可能需要进行更昔洛韦治疗药物监测，以避免毒性增加。
