Abernethy D R, Greenblatt D J
Arch Neurol. 1985 May;42(5):468-71. doi: 10.1001/archneur.1985.04060050066010.
Fourteen obese subjects (mean body weight, 124 kg; percent of ideal body weight [IBW], 178%) and ten control subjects of normal body habitus (mean body weight, 67 kg; 92% IBW) received 300 mg of phenytoin sodium by ten-minute intravenous infusion. Obese subjects compared with controls had prolonged phenytoin elimination half-life (19.9 v 12.0 hours). Total metabolic clearance of phenytoin was greater in obese than in control groups, although the difference was not significant (59 v 39 mL/min). Phenytoin half-life, inversely proportional to clearance and directly proportional to volume of distribution (Vd), was prolonged in obesity mainly as a result of the increase in Vd in obese subjects (84 v 40 L). Phenytoin loading dose should be calculated on the basis of IBW plus the product of 1.33 times the excess weight over IBW. Very obese individuals will require large absolute loading doses of phenytoin to rapidly achieve therapeutic drug concentrations.
十四名肥胖受试者（平均体重124千克；理想体重百分比[IBW]为178%）和十名正常体型的对照受试者（平均体重67千克；92%IBW）通过十分钟静脉输注接受了300毫克苯妥英钠。与对照组相比，肥胖受试者的苯妥英消除半衰期延长（19.9对12.0小时）。肥胖组苯妥英的总代谢清除率高于对照组，尽管差异不显著（59对39毫升/分钟）。苯妥英半衰期与清除率成反比，与分布容积（Vd）成正比，肥胖时苯妥英半衰期延长主要是由于肥胖受试者的Vd增加（84对40升）。苯妥英负荷剂量应根据理想体重加上超出理想体重部分的1.33倍的乘积来计算。极度肥胖的个体需要大剂量的苯妥英绝对负荷剂量才能迅速达到治疗药物浓度。
