Shiue Harn J, Taylor Maria, Sands Kara A
1 Mayo Clinic Hospital, Phoenix, AZ, USA.
2 University of Alabama at Birmingham Hospital, AL, USA.
Ann Pharmacother. 2017 Oct;51(10):862-865. doi: 10.1177/1060028017713294. Epub 2017 Jun 5.
Levetiracetam (LEV) is primarily renally eliminated. In end-stage renal disease (ESRD) patients on hemodialysis (HD), pharmacokinetic studies recommend daily dosing with 50% supplemental doses after 4-hour HD sessions. However, poor medication adherence after HD could result in fluctuating plasma drug levels.
To compare two LEV dosing regimens, daily versus twice-daily (BID), in ESRD patients undergoing HD.
Consecutive ESRD patients (April 2013 to May 2014) receiving maintenance inpatient HD and prescribed LEV prior to admission to our academic tertiary hospital were prospectively analyzed. Demographics, initial lab values, adverse reactions, seizures, and LEV regimens were recorded. LEV levels were obtained pre-HD and post-HD along with levels after receiving post-HD doses. Recovery of plasma levels after HD was assessed by comparison of levels predialysis versus postdialysis and post-HD doses.
We identified 22 patients who met inclusion criteria; 14 BID and 8 daily dosing. Mean predialysis, postdialysis, and post-HD dose plasma levels were higher in patients receiving LEV BID compared with daily (43.1 ± 6.3, 19.4 ± 5.2, 34.9 ± 4.3 vs 21.1 ± 3.9, 6.9 ± 1.5, 11.9 ± 1.7 µg/mL; P < 0.05). BID post-HD levels were 41.9 ± 4.6% of predialysis levels versus 36.9 ± 7.3% with daily dosing ( P = 0.275). Post-HD dose levels were 81.4±4.3% of predialysis on LEV BID versus 65.7 ± 8.8% on LEV daily ( P = 0.045). No seizures were reported during hospital admission in either group.
Compared to LEV daily, BID dosing achieved significantly higher levels and a better recovery to predialysis levels. Although limited by small numbers, a similar relationship between postdialysis levels was not detected.
左乙拉西坦（LEV）主要通过肾脏排泄。在接受血液透析（HD）的终末期肾病（ESRD）患者中，药代动力学研究建议在4小时血液透析疗程后每日给药并补充50%剂量。然而，血液透析后药物依从性差可能导致血浆药物水平波动。
比较接受血液透析的ESRD患者中两种左乙拉西坦给药方案，即每日一次与每日两次（BID）。
对2013年4月至2014年5月期间在我们的学术三级医院住院接受维持性血液透析且入院前已开具左乙拉西坦处方的连续性ESRD患者进行前瞻性分析。记录人口统计学资料、初始实验室值、不良反应、癫痫发作情况及左乙拉西坦给药方案。在血液透析前、后以及接受血液透析后剂量后测定左乙拉西坦水平。通过比较透析前与透析后及血液透析后剂量后的水平来评估血液透析后血浆水平的恢复情况。
我们确定了22例符合纳入标准的患者；14例每日两次给药，8例每日一次给药。接受左乙拉西坦每日两次给药的患者透析前、透析后及血液透析后剂量的血浆平均水平高于每日一次给药的患者（43.1±6.3、19.4±5.2、34.9±4.3与21.1±3.9、6.9±1.5、11.9±1.7μg/mL；P<0.05）。每日两次给药组血液透析后的水平为透析前水平的41.9±4.6%，而每日一次给药组为36.9±7.3%（P = 0.275）。左乙拉西坦每日两次给药组血液透析后剂量水平为透析前的81.4±4.3%，而每日一次给药组为65.7±8.8%（P = 0.045）。两组在住院期间均未报告癫痫发作。
与左乙拉西坦每日一次给药相比，每日两次给药可显著提高血药浓度，并能更好地恢复至透析前水平。尽管样本量有限，但未检测到透析后水平之间的类似关系。
