Berg M J, Fincham R W, Ebert B E, Schottelius D D
College of Pharmacy, University of Iowa, Iowa City 52242.
Epilepsia. 1988 Jan-Feb;29(1):67-73. doi: 10.1111/j.1528-1157.1988.tb05101.x.
The effect of phenytoin (PHT) on serum folate and the effect of additional oral folic acid (FA) on serum folate during continued treatment with PHT were studied in 13 healthy male subjects 20-35 years of age. The study was divided into two phases: Phase I determined Vmax (mg/kg/day) and Km (microgram/ml) of PHT in order to calculate the PHT doses needed for the second phase. Phase II was a four-way cross-over study to examine the effect of 1 and 5 mg FA on total serum PHT concentrations 1 microgram/ml less and 5 micrograms/ml greater than the subject's Km, Km-1 and Km+5, respectively. Both phases examined the effect of PHT on serum folate. In Phase I, serum folate decreased by a mean and standard deviation of 42.15 +/- 21.44% after an average of 24.15 +/- 5.63 days of PHT administration, with a mean steady-state total serum PHT concentration of 8.45 +/- 2.70 micrograms/ml. Mean percentage decreases in serum folate before the addition of 1 and 5 mg FA in Phase II were 12.80 +/- 31.45% and 23.24 +/- 21.24% for Km-1 and Km+5, respectively. The average numbers of days of PHT administration and total serum PHT concentrations before FA administration were 9.52 +/- 3.34 and 15.84 +/- 7.02 days, and 2.60 +/- 2.18 and 8.64 +/- 3.44 micrograms/ml, for Km-1 and Km+5, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
在13名年龄在20至35岁的健康男性受试者中，研究了苯妥英（PHT）对血清叶酸的影响以及在持续服用PHT期间额外口服叶酸（FA）对血清叶酸的影响。该研究分为两个阶段：第一阶段确定PHT的Vmax（mg/kg/天）和Km（微克/毫升），以便计算第二阶段所需的PHT剂量。第二阶段是一项四交叉研究，以检查1毫克和5毫克FA分别对血清总PHT浓度低于和高于受试者Km值1微克/毫升（即Km - 1）和5微克/毫升（即Km + 5）时的影响。两个阶段均检测了PHT对血清叶酸的影响。在第一阶段，平均服用PHT 24.15±5.63天后，血清叶酸平均下降42.15±21.44%，血清PHT稳态总浓度平均为8.45±2.70微克/毫升。在第二阶段，对于Km - 1和Km + 5，添加1毫克和5毫克FA前血清叶酸的平均下降百分比分别为12.80±31.45%和23.24±21.24%。对于Km - 1和Km + 5，服用FA前PHT的平均服用天数和血清PHT总浓度分别为9.52±3.34天和15.84±7.02天，以及2.60±2.18微克/毫升和8.64±3.44微克/毫升。（摘要截选至250字）
