Jacobsen D, Alvik A, Bredesen J E, Brown R D
J Toxicol Clin Toxicol. 1986;24(6):519-31. doi: 10.3109/15563658608995391.
The pharmacokinetics of phenytoin was studied in 4 acute intoxications. Two patients were identical twins aged 2 years 5 months being concomitantly poisoned, whereas one adult male was admitted twice. Their maximal phenytoin plasma concentrations were 246, 200, 168 and 164 mumol/l; the lowest values were in the twins. Despite this, consciousness in the children was more depressed whereas severe ataxia and involuntary movements dominated the course in the adult. All patients survived without any sequelae upon symptomatic treatment. Saturation kinetics of phenytoin could be demonstrated in all cases. For the twins, a Km in the range of 10.3-48.6 mumol/l was calculated, indicating saturation kinetics even within the therapeutic range of 40-80 mumol/l. In the twins, the Vmax was in the range of 47.3-79.4 mumol/l/day with a maximal elimination rate of 37.7-63.6 mumol/l/kg/day. We suggest that these kinetic parameters for phenytoin probably are independent of age.
对4例急性中毒患者的苯妥英药代动力学进行了研究。两名患者是2岁5个月的同卵双胞胎,同时中毒,而一名成年男性被收治了两次。他们的苯妥英血浆最大浓度分别为246、200、168和164μmol/L;最低值出现在双胞胎中。尽管如此,儿童的意识抑制更明显,而成人病程中以严重共济失调和不自主运动为主。所有患者经对症治疗后均存活且无任何后遗症。所有病例均显示苯妥英的饱和动力学。对于双胞胎,计算出的Km在10.3 - 48.6μmol/L范围内,表明即使在40 - 80μmol/L的治疗范围内也存在饱和动力学。双胞胎的Vmax在47.3 - 79.4μmol/L/天范围内,最大消除率为37.7 - 63.6μmol/L/(kg·天)。我们认为这些苯妥英的动力学参数可能与年龄无关。