Medina L, García L, Pérez R, Fernández A, Jung H
Instituto Nacional de Neurología y Neurocirugía, Departamento de Farmacia, Facultad de Química, UNAM, México, DF.
J Pharm Pharmacol. 1998 Dec;50(12):1393-6. doi: 10.1111/j.2042-7158.1998.tb03365.x.
The effect of phenytoin on the disposition of DL-3-hydroxy-3-ethyl-3-phenylpropionamide (HEPP) has been studied in New Zealand white rabbits. Plasma HEPP levels decreased when the drug was administered with phenytoin. The area under the plasma concentration-time curve was reduced by 56.49% (from 43.23+/-7.0 to 18.81+/-2.03 microg h mL(-1)), the elimination half-life was also significantly (P<0.01) reduced (from 2.68+/-0.35 to 1.04+/-0.07 h) and the clearance was increased (from 0.35 to 0.81 L h(-1) kg(-1)). In-vitro protein binding to bovine serum albumin (BSA) and plasma was evaluated by equilibrium dialysis. Plasma protein binding was low (between 33.69 and 37.43% at concentrations ranging from 6.25 to 100 microg mL(-1)). The compound binds preferentially to albumin with an association constant (Ka) of 3.81 x 10(3) M(-1) at 37 degrees C. The results suggest a pharmacokinetic interaction between phenytoin and HEPP, probably on the drug-metabolizing enzyme system in the liver.
已在新西兰白兔中研究了苯妥英对DL-3-羟基-3-乙基-3-苯基丙酰胺（HEPP）处置的影响。当该药物与苯妥英合用时，血浆HEPP水平降低。血浆浓度-时间曲线下面积减少了56.49%（从43.23±7.0降至18.81±2.03μg·h·mL⁻¹），消除半衰期也显著（P<0.01）缩短（从2.68±0.35小时降至1.04±0.07小时），清除率增加（从0.35升至0.81L·h⁻¹·kg⁻¹）。通过平衡透析评估了体外与牛血清白蛋白（BSA）和血浆的蛋白结合情况。血浆蛋白结合率较低（在浓度为6.25至100μg·mL⁻¹范围内，为33.69%至37.43%）。该化合物在37℃时优先与白蛋白结合，结合常数（Ka）为3.81×10³M⁻¹。结果表明苯妥英与HEPP之间存在药代动力学相互作用，可能是在肝脏的药物代谢酶系统上。
