1 Henry Ford Health System, Detroit, MI, USA.
2 University of Michigan College of Pharmacy, Ann Arbor, MI, USA.
Ann Pharmacother. 2019 May;53(5):458-463. doi: 10.1177/1060028018818785. Epub 2018 Dec 7.
Recommended loading doses (LDs) of phenytoin and fosphenytoin range from 10 to 25 mg/kg. Few studies have examined the LD requirements in male versus female patients and in patients who are obese.
To examine the influence of obesity and sex on phenytoin LDs.
This was a retrospective cohort study comparing free phenytoin or fosphenytoin serum concentrations following LDs in male versus female and nonobese versus obese patients. An equation used for determining LDs in obese patients was evaluated.
There were 141 nonobese and 54 obese patients. When adjusted for total body weight, the obese cohort received a smaller LD than the nonobese cohort (17 mg/kg, interquartile range [IQR] = 14.9-20.0, vs 20 mg/kg, IQR = 18.6-20.0, respectively; P < 0.001). There was no difference between the 2 cohorts in the measured free phenytoin concentration following the LD (obese: 1.7 µg/mL [IQR = 1.4-2.0]; nonobese: 1.8 µg/mL [IQR = 1.5-2.1]; P = 0.16). In the obese cohort, men received a significantly lower weight-based phenytoin dose compared with women (15 mg/kg [IQR = 14.0-19.2], vs 19.9 mg/kg [IQR = 15.0-20.0], respectively; P = 0.008). Postload free phenytoin concentrations were similar between the 2 groups (male: 1.6 µg/mL [IQR = 1.2-2.1]; female: 1.7 µg/mL [IQR = 1.4-2.0]; P = 0.24). Conclusion and Relevance: Phenytoin and fosphenytoin LDs of at least 15 mg/kg of actual body weight are more likely to lead to desired free phenytoin concentrations. Obese female patients need a larger weight-based dose than male patients to achieve similar postload phenytoin concentrations.
苯妥英和磷苯妥英的推荐负荷剂量（LD）范围为 10 至 25 毫克/公斤。很少有研究检查男性与女性患者和肥胖患者中 LD 的需求。
检查肥胖和性别对苯妥英 LD 的影响。
这是一项回顾性队列研究，比较了男性与女性和非肥胖与肥胖患者接受 LD 后游离苯妥英或磷苯妥英血清浓度。评估了用于确定肥胖患者 LD 的方程。
有 141 名非肥胖患者和 54 名肥胖患者。当按总体重调整时，肥胖组接受的 LD 小于非肥胖组（17 毫克/公斤，四分位间距[IQR]=14.9-20.0，分别为 20 毫克/公斤，IQR=18.6-20.0；P<0.001）。在 LD 后测量的游离苯妥英浓度方面，两组之间没有差异（肥胖组：1.7μg/mL [IQR=1.4-2.0]；非肥胖组：1.8μg/mL [IQR=1.5-2.1]；P=0.16）。在肥胖组中，男性接受的基于体重的苯妥英剂量明显低于女性（15 毫克/公斤[IQR=14.0-19.2]，分别为 19.9 毫克/公斤[IQR=15.0-20.0]；P=0.008）。两组间的 postload 游离苯妥英浓度相似（男性：1.6μg/mL [IQR=1.2-2.1]；女性：1.7μg/mL [IQR=1.4-2.0]；P=0.24）。结论和相关性：至少 15 毫克/公斤实际体重的苯妥英和磷苯妥英 LD 更有可能导致所需的游离苯妥英浓度。肥胖女性患者需要比男性患者更大的基于体重的剂量才能达到相似的 postload 苯妥英浓度。
