Jarkowski Anthony, Forrest Alan, Sweeney Richard P, Tan Wei, Segal Brahm H, Almyroudis Nikolaos, Wang Eunice S, Wetzler Meir
Department of Pharmacy, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
J Oncol Pharm Pract. 2012 Mar;18(1):91-6. doi: 10.1177/1078155211402107. Epub 2011 Apr 26.
Current vancomycin dosing guidelines in our acute myeloid leukemia population too often achieve suboptimal initial drug concentrations. Our aim was to assess vancomycin pharmacokinetic parameters in acute myeloid leukemia patients and develop an improved dosing equation to attain more accurate initial therapeutic trough levels. Acute myeloid leukemia patients receiving vancomycin for a presumed or documented gram positive infection were eligible. Patients hospitalized in the intensive care unit, those with creatinine clearance <30 mL/min or with limb amputation were excluded. Three samples were collected at the following post-infusion time ranges: 1 h, 3-8 h, and 8-24 h post-infusion, contingent on the dosing interval. Pharmacokinetic data were then fit using a Bayesian-based population pharmacokinetic model. A total of 25 acute myeloid leukemia patients were studied with a mean volume in the central compartment (Vc; L/65 kg), volume of distribution at steady state (Vss; L/65 kg) and distributional clearance (CLd; L/h/65 kg) of 15, 38.9, and 9.32, respectively. CLslope was 0.59 (mg of vancomycin clearance per unit of creatinine clearance in mL/min); this value is 21.4% lower than the established literature value (0.75). The derived equation, based upon these values, was reasonably precise at achieving the desired trough concentration using a priori dosing. The mean (CV%) of the achieved trough was 94% (29%) with a range of 66-188%; 3/25 at <75% and >125%]. We have established that the derived dosing equation can place ≈ 75% of adult acute myeloid leukemia patients at vancomycin trough levels within 75-125% of the target trough level.
目前我们针对急性髓系白血病患者群体的万古霉素给药指南常常导致初始药物浓度未达最佳水平。我们的目的是评估急性髓系白血病患者的万古霉素药代动力学参数，并制定一个改进的给药公式，以实现更准确的初始治疗谷浓度。因疑似或确诊革兰氏阳性感染而接受万古霉素治疗的急性髓系白血病患者符合条件。入住重症监护病房的患者、肌酐清除率<30 mL/分钟的患者或肢体截肢患者被排除在外。根据给药间隔，在输注后以下时间范围采集三个样本：输注后1小时、3 - 8小时和8 - 24小时。然后使用基于贝叶斯的群体药代动力学模型拟合药代动力学数据。共研究了25例急性髓系白血病患者，中央室平均容积（Vc；L/65 kg）、稳态分布容积（Vss；L/65 kg）和分布清除率（CLd；L/h/65 kg）分别为15、38.9和9.32。CL斜率为0.59（每单位肌酐清除率（mL/分钟）的万古霉素清除毫克数）；该值比既定文献值（0.75）低21.4%。基于这些值推导的公式在使用先验给药达到所需谷浓度方面相当精确。达到的谷浓度的平均值（CV%）为94%（29%），范围为66 - 188%；25例中有3例<75%且>125%]。我们已确定，推导的给药公式可使约75%的成年急性髓系白血病患者的万古霉素谷浓度处于目标谷浓度的75 - 125%范围内。
