Department of Pharmacy, City of Hope National Medical Center, Duarte, California 91010, USA.
Pharmacotherapy. 2013 Jan;33(1):22-30. doi: 10.1002/phar.1156.
To evaluate the relationship between voriconazole dose and corresponding serum concentrations in obese and overweight immunocompromised patients.
Retrospective medical record review.
National Cancer Institute-designated comprehensive cancer center.
A total of 92 patients with hematologic malignancies and/or hematopoietic stem cell transplants who received voriconazole and had reported steady-state serum concentrations (peak, random, or trough) during 2005-2010; 124 serum concentrations were available for analysis.
Data on patient demographics, voriconazole concentrations, and other clinical and safety data were collected. Patients were stratified based on body mass index (BMI). Patients with higher BMIs tended to have significantly higher median random voriconazole concentrations with intravenous administration (6.4 mg/L for BMI ≥ 25 kg/m(2) vs 2.8 mg/L for BMI < 25 kg/m(2), p=0.04). This trend was more notable with the intravenous than the oral formulations. With the oral formulation, patients with a BMI of 25 kg/m(2) or greater had a median random concentration of 2.8 mg/L compared with 2.0 mg/L in patients with a BMI less than 25 kg/m(2) (p=0.18). Patients with a BMI of 25 kg/m(2) or greater also had a higher median daily voriconazole dose (640 vs 400 mg, p<0.001). No significant differences were noted in factors that would affect oral absorption of voriconazole (e.g., graft-versus-host disease) among BMI groups. When comparing all voriconazole concentrations, higher concentrations were associated with a greater percentage of patients who had alanine aminotransferase levels of more than 3 times the upper limit of normal. Patients with voriconazole random concentrations of 2 mg/L or greater had higher response rates (50%) than patients with concentrations lower than 2 mg/L (33%).
Standard voriconazole dosing using actual body weight in obese and overweight patients resulted in higher associated serum concentrations. Dosing using adjusted body weight may be necessary in this population in order to achieve optimal concentrations while preventing the potential for increased toxicity.
评估肥胖和超重免疫功能低下患者伏立康唑剂量与相应血清浓度之间的关系。
回顾性病历审查。
国家癌症研究所指定的综合性癌症中心。
2005-2010 年期间共 92 例接受伏立康唑治疗且有稳定期血清浓度（峰、随机或谷值）报告的血液系统恶性肿瘤和/或造血干细胞移植患者；共分析了 124 个血清浓度。
收集了患者人口统计学、伏立康唑浓度以及其他临床和安全性数据。根据体重指数（BMI）对患者进行分层。BMI 较高的患者静脉给药时，随机伏立康唑浓度中位数显著较高（BMI≥25kg/m2 时为 6.4mg/L，BMI<25kg/m2 时为 2.8mg/L，p=0.04）。这种趋势在静脉制剂中比口服制剂更为明显。口服制剂中，BMI≥25kg/m2 的患者随机浓度中位数为 2.8mg/L，而 BMI<25kg/m2 的患者为 2.0mg/L（p=0.18）。BMI≥25kg/m2 的患者也有更高的中位日伏立康唑剂量（640mg 比 400mg，p<0.001）。BMI 组之间，影响伏立康唑口服吸收的因素（如移植物抗宿主病）无显著差异。在比较所有伏立康唑浓度时，浓度较高与丙氨酸氨基转移酶水平超过正常上限 3 倍的患者比例较高相关。随机伏立康唑浓度为 2mg/L 或更高的患者的缓解率（50%）高于浓度低于 2mg/L 的患者（33%）。
在肥胖和超重患者中，使用实际体重的标准伏立康唑剂量会导致更高的相关血清浓度。在该人群中，为了达到最佳浓度并防止潜在的毒性增加，可能需要使用调整后的体重进行剂量。
