Trough ganciclovir concentration as predictor of leukopenia in lung transplant recipients receiving valganciclovir prophylaxis

被引：5

作者：

Katada, Yoshiki ^{[1
,2
]}

Nakagawa, Shunsaku ^{[1
]}

Nagao, Miki ^{[2
,3
]}

Umemura, Keisuke ^{[1
]}

Itohara, Kotaro ^{[1
]}

Nishikawa, Asami ^{[1
,2
]}

Hashi, Sachiyo ^{[1
]}

Katsube, Yurie ^{[1
]}

Hira, Daiki ^{[1
]}

Ohsumi, Akihiro ^{[4
]}

Nakajima, Daisuke ^{[4
]}

Date, Hiroshi ^{[4
]}

Terada, Tomohiro ^{[1
]}

机构：

[1] Kyoto Univ Hosp, Dept Clin Pharmacol & Therapeut, 54 Shogoin Kawahara Cho,Sakyo Ku, Kyoto 6068507, Japan

[2] Kyoto Univ Hosp, Dept Infect Control & Prevent, Sakyo Ku, Kyoto, Japan

[3] Kyoto Univ, Grad Sch Med, Dept Clin Lab Med, Sakyo Ku, Kyoto, Japan

[4] Kyoto Univ, Grad Sch Med, Dept Thorac Surg, Sakyo Ku, Kyoto, Japan

来源：

TRANSPLANT INFECTIOUS DISEASE | 2023年 / 25卷 / 06期

关键词：

Cytomegalovirus; ganciclovir; lung transplantation; prophylaxis; therapeutic drug monitoring; valganciclovir; CYTOMEGALOVIRUS-INFECTION; DOSE VALGANCICLOVIR; PREEMPTIVE THERAPY; PHARMACOKINETICS; MANAGEMENT; OUTCOMES;

D O I：

10.1111/tid.14141

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background: Valganciclovir is the first-line agent for Cytomegalovirus prophylaxis after lung transplantation. However, its use is associated with a relatively high risk of hematological toxicity. This study aimed to investigate the relationship between trough ganciclovir concentration and hematologic toxicity in lung transplantation patients receiving valganciclovir prophylaxis, and identify factors that affect ganciclovir pharmacokinetics in this population. Methods: This prospective observational study included 24 lung transplant patients receiving valganciclovir prophylaxis. The cutoff value of trough ganciclovir concentration was estimated using receiver operating characteristic analysis in leukopenia grade 3 and higher. Population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling program. Results: The trough ganciclovir concentration was significantly higher in the group with leukopenia grades 3 or higher than in the group with grades less than or equal to 2 (1605.7 +/- 860.1 ng/mL [n = 3] vs. 380.5 +/- 175.8 ng/mL (n = 21), p < .001). The cutoff value of trough ganciclovir concentration for predicting greater than or equal to grade 3 leukopenia was estimated as 872.0 ng/mL. Creatinine clearance and lung re-transplantation were found to have a significant impact on the total body clearance of valganciclovir. Ganciclovir clearance was decreased in patients with reduced creatine clearance or re-transplantation. Conclusion: These results suggest that higher ganciclovir trough concentrations are associated with an increased risk of leukopenia grade 3 or higher, and that creatinine clearance and lung re-transplantation affected the pharmacokinetics of ganciclovir.

引用

页数：9

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