Clark Sarah L, Leloux Megan R, Dierkhising Ross A, Cascino Gregory D, Hocker Sara E
Mayo Clinic, Rochester, MN.
Neurol Clin Pract. 2017 Feb;7(1):45-52. doi: 10.1212/CPJ.0000000000000322.
Previous studies evaluated the disposition of IV phenytoin loading doses and found that obese patients had increased drug distribution into excess body weight, larger volumes of distribution, and longer half-lives when compared to their nonobese counterparts. We assess the safety and efficacy of fosphenytoin loading doses in patients with different body mass indices (BMIs).
A retrospective chart review was conducted in 410 patients who received fosphenytoin. Patients were divided into 2 groups: BMI <30 (nonobese) and BMI ≥30 (obese). Patient demographics, fosphenytoin dose administered in mg/kg body weight, renal and liver function tests, fosphenytoin drug levels, and pre- and post-fosphenytoin administration vital signs were collected to assess for adverse events. Necessity of additional antiepileptic loading doses was used as a surrogate for clinical efficacy.
The median dose of fosphenytoin administered was 19 mg/kg (interquartile range 15-20). The most frequently encountered adverse event was hypotension, which occurred in 39% of the cohort. Using a Bonferroni adjustment for multiple comparisons, there were no differences in adverse events between the 2 groups. The need for additional antiepileptic loading doses was not different between the 2 groups ( = 0.07).
The incidence of adverse events and the need for repeat loading antiepileptic medications was similar between the 2 groups. From our findings, the patients in our study did not receive empiric loading dose adjustments and the current method of loading fosphenytoin achieves similar outcomes, regardless of the patient's BMI.
既往研究评估了静脉注射苯妥英钠负荷剂量的处置情况,发现与非肥胖患者相比,肥胖患者药物向多余体重的分布增加、分布容积更大且半衰期更长。我们评估了不同体重指数(BMI)患者使用磷苯妥英钠负荷剂量的安全性和有效性。
对410例接受磷苯妥英钠治疗的患者进行回顾性病历审查。患者分为两组:BMI<30(非肥胖)和BMI≥30(肥胖)。收集患者人口统计学资料、以mg/kg体重计的磷苯妥英钠给药剂量、肾功能和肝功能检查、磷苯妥英钠药物水平以及磷苯妥英钠给药前后的生命体征,以评估不良事件。额外抗癫痫负荷剂量的必要性用作临床疗效的替代指标。
磷苯妥英钠的中位给药剂量为19mg/kg(四分位间距15 - 20)。最常出现的不良事件是低血压,在该队列中发生率为39%。采用Bonferroni校正进行多重比较时,两组之间不良事件无差异。两组之间额外抗癫痫负荷剂量的需求无差异(P = 0.07)。
两组之间不良事件的发生率以及重复给予负荷量抗癫痫药物的需求相似。根据我们的研究结果,我们研究中的患者未接受经验性负荷剂量调整,且目前磷苯妥英钠的负荷给药方法取得了相似的结果,无论患者的BMI如何。