Miller Calvin L, Winans S Alexander, Veillette John J, Forland Steven C
J Pediatr Pharmacol Ther. 2018 Mar-Apr;23(2):92-99. doi: 10.5863/1551-6776-23.2.92.
Optimization of vancomycin dosing is difficult in children, given rapid drug clearance and patient heterogeneity. We sought to evaluate the impact of dosing using individual pharmacokinetic parameters on time to goal trough concentration in pediatric oncology patients.
A retrospective review was conducted to assess vancomycin dosing in the pediatric oncology unit at Loma Linda University Children's Hospital between January 2013 and August 2013 (standard dosing group [SDG]). These patients were compared to those in a prospective arm that used pharmacokinetic dosing (pharmacokinetic dosing group [PKG]) between March 2014 and May 2015. Outcomes included percent of patients reaching a target trough by the specified time points, number of dose adjustments, number of serum concentrations drawn, and number of patients with supratherapeutic troughs.
Of 35 patients meeting inclusion criteria for the SDG, 2 (5.7%) reached goal trough concentration by 48 hours, compared with 14 of 16 patients (87%) in the PKG (p = 0.0001). Significantly more patients reached their goal trough at each time point in the PKG. There was no difference in number of dose adjustments, but significantly more concentrations were drawn on average in the PKG (mean, 4.6 versus 3.1, p = 0.02). In the SDG and PKG, respectively, 1 patient and 3 patients had supratherapeutic trough concentrations (p = 0.09).
Dosing using individual pharmacokinetic parameters led to a significant reduction in time to attain the desired vancomycin trough concentration in our pediatric oncology patients. Given the wide variation in dose requirements in this and other studies, application of patient-specific pharmacokinetics is essential to optimize vancomycin dosing in pediatric patients.
鉴于药物清除迅速且患者存在异质性,儿童万古霉素给药方案的优化颇具难度。我们试图评估依据个体药代动力学参数给药对儿科肿瘤患者达到目标谷浓度时间的影响。
进行了一项回顾性研究,以评估2013年1月至2013年8月期间洛马林达大学儿童医院儿科肿瘤病房的万古霉素给药情况(标准给药组[SDG])。将这些患者与2014年3月至2015年5月期间采用药代动力学给药的前瞻性队列中的患者进行比较(药代动力学给药组[PKG])。结果包括在特定时间点达到目标谷浓度的患者百分比、剂量调整次数、采血样测定血清浓度的次数以及谷浓度高于治疗范围的患者数量。
符合SDG纳入标准的35例患者中,2例(5.7%)在48小时内达到目标谷浓度,而PKG的16例患者中有14例(87%)达到目标谷浓度(p = 0.0001)。在每个时间点,PKG中有显著更多患者达到目标谷浓度。剂量调整次数无差异,但PKG平均采血样测定血清浓度的次数显著更多(平均4.6次对3.1次,p = 0.02)。在SDG和PKG中,分别有1例和3例患者谷浓度高于治疗范围(p = 0.09)。
依据个体药代动力学参数给药可显著缩短我们儿科肿瘤患者达到理想万古霉素谷浓度的时间。鉴于本研究及其他研究中剂量需求差异很大,应用患者特异性药代动力学对于优化儿科患者万古霉素给药至关重要。